Adjustable Medium Diverter

ABSTRACT

A system for modulating delivery of a fluid medium to a selected site within a patient&#39;s body includes a syringe for injecting the fluid medium, a delivery catheter including a conduit for delivering the fluid medium from outside of the body to the selected site within the body, and a flow diverter assembly disposed in a fluid medium flow path between the syringe and the delivery catheter. The syringe includes a chamber for receiving the fluid medium therein. The flow diverter assembly is configured to simultaneously divert at least some of the fluid medium within the chamber of the syringe away from the delivery of the medium through the delivery catheter conduit during injecting with the syringe, and wherein the flow diverter assembly creates increasing medium fluid flow resistance with increasing pressure level of the fluid medium within the flow diverter assembly. A method for modulating fluid delivery to a selected site within a patient&#39;s body is also disclosed.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority from U.S. ProvisionalPatent Application No. 62/048,974, filed Sep. 11, 2014, for “Devices andMethods for Modulating Medium Delivery,” and U.S. Provisional PatentApplication No. 62/082,260, filed Nov. 20, 2014, for “Devices andMethods for Modulating Medium Delivery.” Both of these priorityapplications are incorporated by reference in their entirety.

BACKGROUND

There are numerous occasions in the diagnostic, prophylactic andtreatment practice of medicine wherein an agent, medicant, or medium ispreferably delivered to a specific site within the body, as opposed to amore general, systemic introduction. One such exemplary occasion is thedelivery of contrast media to coronary vasculature in the diagnosis(i.e., angiography) and treatment (i.e., balloon angioplasty andstenting) of coronary vascular disease.

SUMMARY

In one aspect, a system for modulating delivery of a fluid medium to aselected site within a patient's body is disclosed. The system comprisesa syringe for injecting the fluid medium, a delivery catheter comprisinga conduit for delivering the fluid medium from outside of the body tothe selected site within the body, and a flow diverter assembly disposedin a fluid medium flow path between the syringe and the deliverycatheter. The syringe comprises a chamber for receiving the fluid mediumtherein. The flow diverter assembly is configured to simultaneouslydivert at least some of the fluid medium within the chamber of thesyringe away from the delivery of the medium through the deliverycatheter conduit during injecting with the syringe, and wherein the flowdiverter assembly creates increasing medium fluid flow resistance withincreasing pressure level of the fluid medium within the flow diverterassembly.

In another aspect, a method for modulating fluid delivery of a fluidmedium to a selected site within a patient's body is disclosed. Themethod comprises injecting the fluid medium from a syringe through afluid delivery catheter to deliver the fluid medium to the selectedsite, and simultaneously employing a flow diverter assembly disposed ina fluid medium flow path between the syringe and the delivery catheter.The flow diverter assembly resides outside the patient's body and isconfigured to divert at least some of the fluid medium within thesyringe away from the delivery of medium to the delivery catheterconduit during injection of medium, and wherein the diverter assembly isconfigured to increase medium fluid flow resistance with an increase inpressure level of the fluid medium within the flow diverter assembly.

This summary is provided to introduce concepts in simplified form thatare further described below in the Detailed Description. This summary isnot intended to identify key features or essential features of thedisclosed or claimed subject matter and is not intended to describe eachdisclosed embodiment or every implementation of the disclosed or claimedsubject matter. Specifically, features disclosed herein with respect toone embodiment may be equally applicable to another. Further, thissummary is not intended to be used as an aid in determining the scope ofthe claimed subject matter. Many other novel advantages, features, andrelationships will become apparent as this description proceeds. Thefigures and the description that follow more particularly exemplifyillustrative embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosed subject matter will be further explained with reference tothe attached figures, wherein like structure or system elements arereferred to by like reference numerals throughout the several views.

FIG. 1 illustrates in graphic form, the exemplary pulsatile nature ofleft coronary artery blood flow and blood pressure.

FIG. 2 is a graphic representation of an exemplary blood flow rateprofile for a left main coronary artery.

FIG. 3A illustrates an exemplary coronary artery treatment system.

FIG. 3B illustrates a distal portion of the exemplary treatment of FIG.3A.

FIG. 3C illustrates a proximal portion of the exemplary treatment systemof FIG. 3A.

FIG. 4A illustrates graphically an exemplary injection profile (flowrate) of agent for the treatment system of FIG. 3.

FIG. 4B illustrates graphically an injection profile (flow rate) ofagent for the treatment system of FIG. 3, identifying under-injectionand over-injection volume areas of media for opacification purposes.

FIG. 4C illustrates graphically an exemplary improved constant injectionprofile (flow rate) of agent for achieving opacification.

FIG. 4D illustrates graphically the exemplary agent injection profile ofFIG. 4A relative to the exemplary blood rate flow profile of FIG. 2.

FIG. 5A illustrates an exemplary flow of injection in the distal portionof the exemplary treatment system of FIG. 3B.

FIG. 5B illustrates an alternative exemplary flow of injection in thedistal portion of the exemplary treatment system of FIG. 3B.

FIGS. 6A and 6B illustrate an exemplary single chamber flow modulator,in different stages of flow control.

FIG. 6C illustrates the single chamber flow modulator of FIGS. 6A and 6Bdisposed in the proximal portion of the treatment system of FIG. 3.

FIG. 7 sets forth exemplary fluid flow equations (laminar) that may beused in modeling a conduit fluid flow.

FIGS. 8A, 8B and 8C illustrate an exemplary two-chamber flow modulator,in different stages of flow control.

FIGS. 9A, 9B and 9C illustrate an exemplary two-chamber flow modulatorwith holding chamber, in different stages of flow control.

FIGS. 10A and 10B illustrate a capacitance chamber flow modulator(bladder), in different stages of flow control.

FIGS. 11B and 11B illustrate an exemplary flow modulator with constantforce chamber, in different stages of flow control.

FIGS. 12A and 12B illustrate an exemplary constant flow modulator, indifferent stages of flow control.

FIG. 13 illustrates graphically an exemplary agent injection profile(flow rate) synchronized with the exemplary blood flow rate profile ofFIG. 2.

FIG. 14 illustrates exemplary schemas of synchronized agent deliverymodulation systems.

FIG. 15 illustrates an exemplary synchronized agent delivery with directmodulation.

FIG. 16A illustrates an exemplary synchronized agent delivery withindirect modulation, adjacent a distal portion of a treatment systemtherefor.

FIG. 16B illustrates an exemplary synchronized agent delivery withindirect modulation (top view), adjacent a proximal portion of such atreatment system.

FIG. 16C illustrates an exemplary synchronized agent delivery withindirect modulation (side view), adjacent a proximal portion of such atreatment system.

FIG. 16D illustrates, in side sectional view, the brake mechanism of theexemplary synchronized agent delivery arrangement of FIG. 16C.

FIGS. 17A, 17B, 17C and 17D illustrate exemplary delivery catheterdistal constructions.

FIG. 18 illustrates an exemplary delivery catheter with distaldisrupting structure.

FIG. 19 illustrates, in chart form, exemplary medium delivery modulationcontrol factors and/or elements, the features of which may be combined,in part or in whole, to achieve the advantages of minimizingover-introduction of agent into a patient, pursuant to the teachingsdisclosed herein.

FIGS. 20-22 illustrate an exemplary constant force modulator system, indifferent stages of flow control.

FIGS. 23, 24A and 24B illustrate an exemplary passive blood flow andmedium flow valving mechanism operable as a function of a physicalattribute in and/or around a medium delivery site.

FIGS. 25A and 25B illustrate another exemplary arrangement for passivevalve control of blood flow and medium flow adjacent a medium deliverysite.

FIG. 26 illustrates an exemplary variable force delivery platform foruse in a modulator system.

FIG. 27 illustrates a force pin selection guide for use in connectionwith a variable force delivery platform.

FIG. 28 illustrates an exemplary pin and its associated pin locationslot, as used with a variable force delivery platform.

FIG. 29 illustrates an alternative exemplary variable force deliveryplatform for use in a modulator system.

FIG. 30 illustrates an exemplary flow diverter assembly.

FIG. 31 illustrates a switch plate for the flow divert assembly of FIG.30.

FIG. 32 illustrates an exemplary flow restrictor assembly.

FIG. 33 illustrates an exemplary automatic flow diverter assembly.

FIG. 34 is an exploded perspective view of the automatic flow diverterassembly of FIG. 33.

FIG. 35 is a sectional view of a valve in the automatic flow diverterassembly of FIGS. 33 and 34.

FIG. 36 is an enlarged perspective view of a portion of FIG. 35.

FIG. 37 is a perspective view of an exemplary compression plate for thevalve of the automatic flow diverter assembly shown in FIGS. 33-36.

FIG. 38 is a plan view of a proximal face of the compression plate ofFIG. 37.

FIG. 39 is a side view, as taken along lines 39-39 in FIG. 38.

FIG. 40 is a sectional view, as taken along lines 40-40 in FIG. 38.

FIG. 41 is a sectional view, as taken along lines 41-41 in FIG. 38.

FIG. 42 is an exploded perspective view of an alternative automatic flowdiverter assembly.

FIG. 43 is a side view of a movable diffuser and check valve O-ringthereon for the automatic flow diverter assembly of FIG. 42.

FIG. 44 illustrates graphically a typical injection profile (pressure)of agent with a treatment system of FIG. 3, and an injection profile(pressure) of agent for the treatment system of FIG. 3 as modulatedusing a variable force delivery platform such as illustrated in FIGS.26-27.

FIG. 45 illustrates graphically an injection profile (pressure) of agentfor the treatment system of FIG. 3 in a typical injection (P_(Typical))and a pulsed medium injection profile (P_(Pulsatile I)).

FIG. 46 illustrates an enlarged view a segment of the pulsed injectionprofile P_(Pulsatile I) of FIG. 45.

FIG. 47 illustrates graphically an injection profile (pressure) of agentfor the treatment system of FIG. 3 in a typical injection (P_(Typical))and an alternative pulsed medium injection profile (P_(Pulsatile II)).

FIG. 48 illustrates an enlarged view a segment of the pulsed injectionprofile P_(Pulsatile II) of FIG. 47.

FIG. 49 illustrates an exemplary arrangement for indirect application ofpulsed pressure to medium being manually injected via a catheter.

FIG. 50 illustrates an exemplary arrangement for direct application ofpulsed pressure to the medium being manually injected via a catheter.

FIGS. 51A, 51B and 51C schematically illustrate alternate flow diversionconfigurations for agent flow from an injector through a cathetersystem.

FIG. 52 illustrates an exemplary medium management system.

FIG. 53 is a perspective view of an exemplary medium diversionreservoir.

FIG. 54 is a perspective exploded view of an exemplary medium diversionreservoir.

FIG. 55 is a cross-sectional view of the exemplary medium diversionreservoir in a first configuration, taken along line 55-55 of FIG. 53.

FIG. 56 is a cross-sectional view of the exemplary medium diversionreservoir in a second configuration, taken along line 55-55 of FIG. 53.

FIG. 57 illustrates another exemplary medium diversion reservoir.

FIG. 58 illustrates another exemplary medium management system.

While the above-identified figures set forth one or more embodiments ofthe disclosed subject matter, other embodiments are also contemplated,as noted in the disclosure. In all cases, this disclosure presents thedisclosed subject matter by way of representation and not limitation. Itshould be understood that numerous other modifications and embodimentscan be devised by those skilled in the art which fall within the scopeand spirit of the principles of this disclosure.

The figures may not be drawn to scale. In particular, some features maybe enlarged relative to other features for clarity. Moreover, whereterms such as above, below, over, under, top, bottom, side, right, left,etc., are used, it is to be understood that they are used only for easeof understanding the description. It is contemplated that structures maybe oriented otherwise.

DETAILED DESCRIPTION

This disclosure pertains to devices and methods used to control,transform or otherwise modulate the delivery of a substance, such asradiopaque contrast, to a delivery site. More specifically, it is theintention of the following devices and methods to modulate the deliveryof media to a vessel, vascular bed, organ, or/and other corporealstructures so as optimize the delivery of media to the intended site,while reducing inadvertent introduction (or reflux) of the media toother vessels, vascular beds, organs, and/or other structures, includingsystemic introduction.

The terms medium (media), agent, substance, material, medicament, andthe like, are used generically herein to describe a variety of fluidalmaterials that may comprise, at least in part, a substance used in theperformance of a diagnostic, therapeutic or/and prophylactic medicalprocedure and such use is not intended to be limiting.

The description, as well as the inventive devices and methods describedherein, may be used in modulating contrast media delivery to thecoronary vasculature in prevention of toxic systemic effects of such anagent; although, one skilled in the art would recognize that there aremany other applications wherein the controlled delivery of a media to aspecific vessel/structure/organ/site of the body may also benefit fromthe devices and methods disclosed herein. For simplicity, these devicesand methods may be described as they relate to contrast media deliverymodulation. As such, they may be used in the prevention of ContrastInduced Nephropathy; however, it is not intended, nor should it beconstrued, so as to limit the use to this sole purpose. Exemplary otheruses may include the delivery/injection/modulation of: cancer treatmentagent to a tumor; thrombolytic to an occluded artery; occluding orsclerosing agent to a vascular malformation or diseased tissue; geneticagent to a muscular bed, neural cavity or organ; emulsion to the eye;bulking agent to musculature and/or sphincter; imaging agent to thelymphatic system; anti-biotics to an infected tissue; supplements in thedialysis of the kidney; to name but a few.

Exemplary Use—Prevention of Contrast Induced Nephropathy

Contrast Induced Nephropathy (CIN) is a form of kidney damage caused bythe toxic effects of dyes (radiopaque contrast media) used, for example,by cardiologists to image the heart and its blood vessels duringcommonly performed heart procedures, such as angiography, angioplasty,and stenting. In general, the dye is toxic and is known to damagekidneys. Although most healthy patients tolerate some amount of the“toxicity,” patients with poor or non-functioning kidneys may sufferfrom rapidly declining health, poor quality of life, and significantlyshortened life expectancy. Potential consequences of CIN include:irreversible damage to the kidneys; longer hospital stays; increasedrisk of heart disease; increased risk of long-term dialysis; and,ultimately a higher mortality risk. For patients who acquire CIN, theirrisk of dying remains higher than others without CIN, and this riskcontinues even after five years of their procedure. CIN has asignificant economic burden on the healthcare system and currently thereis no treatment available to reverse or improve damage to the kidneys,once a patient develops CIN.

To date, there have been attempts in reducing the toxic effects ofcontrast media on patients who undergo procedures involving dyes,especially those patients who are at high risk for developing CIN. Someof these efforts have been to: change the inherent toxicity(chemical/molecular nature) of the dyes; reduce the total amount ofcontrast agent injected (through injection management and/or dyeconcentration); remove media through coronary vasculature isolation andblood/contrast agent collection systems, to name a few. These methodsand/or devices used in the control of the toxic effects of contrastagents have had their inherent compromises in effectively delivering acontrast media specifically to a target site while minimizing thesystemic effects. As an example, changing the composition of a dyeand/or injection concentration may help reduce a contrast agent'sinherent toxicity at the expense of the contrast agent's ability toperform its intended function (e.g., visualization of vasculature).Conversely, the ability to “collect” contrast agent laden blood“downstream” from the visualization site may ensure visualization, butrequires the complexity of placement and operation of a collectionsystem.

Other attempts to manage the amount of contrast agent delivered to apatient have employed automated (versus manual, syringe injected)contrast media injection systems. Close monitoring and control of thetotal quantity of contrast agent injected may have a positive impact inthe incidence of CIN. However, these injection systems are expensive(including capital equipment and disposables), cumbersome to use withina cath lab, and take additional time and expertise to set-up and operateproperly. Improper use could negate any benefits seen by bettermanagement of the quantity of the contrast agent delivered to a patient,and the additional time required to set-up such a system may also addsignificant complexity to a procedure.

Exemplary Use—Coronary Blood Flow and Management of Agent Delivery

Many of the vascular structures and capillary beds of the human bodyperfuse with enriched, oxygenated blood as a result of the blood beingpressurized by the cyclical driving force of the heart duringcontraction (systole) and decompression (diastole). Most vascular bloodflows peak in the body in response to the heart's contractile phase.Because of the cyclical flow of blood in the vasculature, optimizationof delivery of any contrast agent to a vascular delivery site may beenhanced through the coordination of an injection's pressure and flow tocoincide more closely with that of the vascular site receiving thecontrast agent.

Although similar flow principals may apply, the flow of coronary bloodis unique in that the perfusion of the heart coronary arteriesprincipally peak during the diastolic (relaxation) phase of theventricular cycle. As seen in FIG. 1, the pressure of blood in the aorta(from the heart) peaks during ejection (b). However, the flow of bloodinto the coronary arteries (left coronary artery/left main, as anexample) actually peaks after this, during the relaxation/decompressionof the heart (i.e., during diastole (c)). Thus, blood flow through thecoronary vasculature, in a normal functioning heart, peaks when aorticblood pressure has diminished. This phenomenon appears contra to whatone would expect for arterial heart vessel filling. The flow of bloodthrough the coronary vasculature is not necessarily, or completely,“driven” by a high pressure gradient in the aorta into the coronaryarteries. In fact, normally the filling of the coronary arteries peakswhen the pressure in the aorta is substantially lower than the peaksystolic pressure.

It is believed that this phenomenon is derived from a backwardtravelling, “driving force” or “suction” force of blood that isgenerated by the relaxing of the myocardium (as well as myocardialmicrovasculature) during diastole—in essence, during the decompressionof the heart. The decompression of the heart in diastole results in adriving wave caused by the relief of the myocardial compression. Thisforce is actually created through a pressure gradient wherein the lowpressure of the aorta is actually higher than the vacuum created in thecoronary capillary beds—thus, a gradient created from the aorta to themicrovasculature. Further description of this phenomenon may be found,for example, in “Evidence of a Dominant Backward-Propagating ‘Suction’Wave Responsible for Diastolic Coronary Filling in Humans, Attenuated inLeft Ventricular Hypertrophy” (Circulation. 2006; 113:1768-1778), whichis incorporated by reference in its entirety herein.

A challenge in the delivery of contrast agent to the coronary arteriesis the cyclical nature of the flow in the arteries (quantity and rate).As further seen in FIG. 1, the pulsatile blood in the arteries maychange significantly in flow rate over a single cycle of the heart. Inaddition, the variation in flow rate transpires over a very short periodof time—in many cases, this takes place in less than a second.

FIG. 2 illustrates an example of a blood flow pattern that may be foundwithin a left main coronary artery of a human heart. The illustratedprofile of blood flow rate (Q_(Blood), or blood volume flow rate)represents about four cycles of the heart over a period of time that isless than four seconds. The average flow rate of blood (e.g., meanQ_(Blood)) in this example averages about 3.7 ml/sec over a single cycleof the heart, and may vary significantly during each cycle from about1.3 ml/sec to about 6.5 ml/sec. In this example, the left main isapproximately 4.4 mm diametrically and has a length about 5 mm before itbifurcates into the left anterior descending artery and the leftcircumflex artery. It should be noted that this is only an example andany physiological, anatomical, or fluid flow characteristics describedmay vary significantly between patients, as well as within the samepatient. These variations may occur as a function of age, vascularand/or coronary disease, vascularity and collateralization of the heart,metabolism, blood pressure, patient activity, stress level, functionalstatus of various patients' organs, patient weight, vasodilatory and/orconstrictive medicants, and chemical or biochemical mediators, to namebut a few of the involved variables. Therefore, the example is intendedto help elucidate the disclosure of the devices and methods herein, andis not intended to limit their use.

In further illustrating the inventive devices and methods herein, anexample of a use of the system will involve the delivery of contrastagent to the left arterial system of the heart during the performance ofa treatment procedure (e.g., stent delivery). However, this exemplaryuse should not, in any way, limit the use of the devices and methodsdescribed.

Referring to FIG. 3A, a catheter, therapy, or treatment system 10 isshown that may be used in the treatment of an occlusion in a coronaryvessel. FIG. 3B further highlights the distal portion of the cathetersystem, proximate a left coronary artery ostium. As seen in FIG. 3B, thesystem 10 includes a system delivery catheter 12 (e.g., guide catheter)and occlusion treatment devices (e.g., balloon catheter 14 with stent 16and guide wire 18). The distal end of the guide catheter 12 is placedproximate an opening 20 (ostium) of the aorta 22 to the left coronaryartery 24 (left main), off of the aortic root 26. The system 10 may beplaced by percutaneous advancement of the system 10 from the femoralartery (not shown) to the aortic root 26. FIG. 3C further illustrates aproximal portion of such an arterial occlusion treatment system 10(including a balloon catheter with stent, guide wire, connectors, etc.)shown in FIGS. 3A and 3B. Typically, there is a guide catheter connector28 that may have a Tuoy-Borst compression fitting 30 attached to aproximal portion of the connector 28. The treatment devices may bepassed axially through an outlet of the connector 30 and into a primarylumen 32 of the connector 28, and then into the guide catheter 12. Thefitting 30 of the connector 28 may be adjusted so as to allow passage ofthe treatment devices through connector 28, but resist back flow offluid out of the guide catheter 12 and connector 28. In addition, theconnector 28 may have a secondary lumen 34 displaced laterally of, andin communication with, primary lumen 32. Secondary lumen 34 mayterminate in luer-fitting 36. A manifold assembly 38 with multiple ports(e.g., ports 38 a, 38 b) may be attached to luer fitting 36. Theseadditional ports of the manifold 38 may be used to infuse various mediathrough the guide catheter 12 (e.g., within a flow conduit defined by aninner lumen of the guide catheter, and the outer proximities of anytreatment system components 14, 16, 18 therein). Such infusions mayinclude, for example, radiopaque contrast, medicaments, or saline forflushing the guide catheter 12.

The treatment system 10 described in FIGS. 3A-3C may be comprised ofcomponents that may be used in such a procedure, such as a 6 F guidecatheter having an approximate length of 100 cm and an inner diameter ofapproximately 0.070 inch. Further, the treatment devices (e.g., ballooncatheter, stent, guide wire, etc.) might have an outer diameter of 3.2 Fproximally and 2.7 F distally. The delivery of the treatment devices maybe accomplished by passing the balloon catheter through the guidecatheter and over a guide wire of 0.014 inch in diameter. The injectionof contrast agent for the visual assessment of the vasculature may beperformed by activating an injection device 40 (such as an injector orsyringe), as seen in FIG. 3C. In this case, the contrast agent may passfrom the injection device 40, through a tubing connector 42 (i.e.,between injection device 40 and manifold 38), the manifold 38, the guidecatheter connector 28, and ultimately through the co-axial conduitdefined between the guide catheter inner diameter and the treatmentcatheter system (e.g., balloon catheter) outer diameter.

This example is illustrative of a treatment procedure and should not belimited to the various assemblies that may be deployed for any givenprocedure, or by any specific physician. The various infusions of thegiven example may be introduced through the manifold connections bynumerous means, to include manual injection (i.e., syringe), automaticinjection with an injection machine, or a “gravity fed” injectionarrangement. How perfusions/infusions of various substances may beadministered may depend on the medium and the intended therapy. In FIG.3C, a syringe is shown connected to the manifold with a tubingconnector, providing means to hand-inject contrast medium through themanifold and to the distal outlet of the guide catheter. Conversely, apower injector may be attached to the manifold to perform the injection,as an alternative configuration.

Moreover, the example described is illustrative of a treatment procedurecomprising a “guide catheter” in conjunction with a treatment system.However, there are a multitude of constructions of conduits that may becapable of delivering, or otherwise mediating the delivery, of substancefrom a proximal portion of a system (outside of a body) to an intendedcorporeal site. And thus, reference to a “guide catheter” or “catheter”in the example could be described as a tube, delivery catheter, or anyother conduit used in mediating the delivery of a substance; and assuch, should not be limited to the various assemblies for the exemplaryprocedure.

FIG. 4A illustrates an exemplary hand-injection flow rate profile(Q_(Agent)) of contrast media that may be delivered through a cathetertreatment system such as described above. In the example of FIG. 4A,flow rate (Q_(Agent)) is described. However, it should be apparent tothose skilled in the art that a pressure profile could have been used todescribe the concepts herein since there is a direct relationshipbetween the flow rate (Q) and the pressure drop (dP or ΔP) over aconduit.

In the example of FIG. 4A, an injection profile of Q_(Agent), asdelivered to the distal tip of the guide catheter, representsapproximately 10-12 ml of contrast media injected over approximately 3-4seconds. This may be a fairly typical hand-injection for illuminatingthe left coronary vasculature over 2 to 5 cycles of the heart (whileperforming a stenting procedure); although, such injections may varysignificantly (e.g., from 3 ml to 30 ml over periods of 1 to 8 seconds).It should be noted that some clinical investigators (and injectormanufacturers) have suggested using around 5 ml/second flow rate ofagent (Q_(Agent)) for a left heart injection. However, theserecommendations may have been derived solely on the optimization ofvessel opacification, with little regard for over-use of contrast media.Over-injection may result in unnecessary delivery of contrast mediasystemically. It is the objective of at least some of the embodimentsherein to modulate systemic contrast induction, and therefore minimize“over-injection” (injection that is greater than necessary for thecontrast agent to effectively perform its opacification function).

In a coronary angiography procedure, a hand-injection is normallyadministered with increasing pressure, and thus volume, until contrastmedia is “seen” filling the coronary vasculature radiographically. Atthis point, the administration continues for about 3 seconds until thequantity of contrast media (e.g., approximately 10 ml) within theinjector is used. For an automatic injector, typically the pressure orvolume may be set (e.g., 5 ml/sec) and then the operator may activatethe automatic injector with a hand-held actuator for several cycles ofthe heart.

The exemplary injection profile Q_(Agent) shown in FIG. 4A reveals anincreasing injection (flow rate, which is directly related to pressure).V_(i) on the graph of FIG. 4A represents a minimum level of injectionflow rate that may be necessary for the operator to “see” vascularity asa result of visualizing the contrast medium. In essence, V_(i) is aninjection rate of media that may be delivered to a vessel, or organ,wherein V_(i) is a level known, or believed to be, an acceptableconcentration of the substance to provide its intended function. In thiscase, V_(i) is the level of delivery wherein the concentration ofcontrast media injected to the left main is of sufficient quantity toopacify the vasculature, on the average, over several cycles of theheart. V_(i), as shown in this example, is approximately 3.0 ml/second.That is to say, with an injection of a constant 3.0 ml/second ofcontrast media the operator may effectively visualize the vasculature,while not over-injecting contrast media. In this exemplary context, aninjection meaningfully less than V_(i) will not provide adequateopacification. The exemplary injection of profile Q_(Agent) in FIG. 4Aresults in a total volume of approximately 11 ml of contrast mediadelivered.

Referring to FIG. 4B, various areas are shown which may have (bydefinition of V_(i)) injection flows that are either insufficient toopacify the vessel appropriately (areas A and B), or are of a magnitudegreater than is necessary for opacification, and may thus result in theover-delivering of contrast agent (area C). That is to say, if theinjection had been controlled in the delivery of the contrast agent toobtain V_(i) (identified as a rectangle within the injection rateprofile Q_(Agent) of FIG. 4B), approximately 3 ml less of contrast (25%to 30%) might have been used to achieve the same result (e.g., tosufficiently visualize the artery over the same period of time).Therefore, an injection flow rate profile Q_(Improved) shown in FIG. 4Cmay outline an “improved” constant flow rate of injection for V_(i)(i.e., wherein the injection flow rate may be held at a constant ratesufficient for visualization).

As a practical matter, and in further illustration of the complexity inefficiently delivering contrast agent into the dynamic environment of acoronary artery, some operators of the injector (a syringe, for example)may try to mimic a rapid injection so as to minimize the area of A inFIG. 4B through a rapid increase of pressure (and commensurate volumeflow rate) with an injection. When sufficient opacification is “seen”radiographically, the operator may then decrease the pressure (andvolume flow rate) of the injection. This technique may be helpful inreducing the area of A (quickly reaching V_(i)); however, the operatormay “over-shoot” the delivery rate required to the vessel foropacification (i.e., V_(i)) and thus increase the amount ofover-injection which may be seen by area C in FIG. 4B. It should benoted that a 10 cc (ml) syringe may be capable of injecting at 100 psior more. This pressure of injection from the syringe could generateflows as high as 4.0 ml/second in the exemplary system described above;whereas, only 75 to 85 psi may be needed to inject 3.0 ml/second, as anexample.

FIG. 4D illustrates the exemplary flow of blood in the left main (e.g.,left main 24 of FIG. 2), noted as blood flow rate profile Q_(Blood)super-imposed with an exemplary profile of an injection flow rate ofcontrast (e.g., profile Q_(Agent) of FIGS. 4A and 4B) over-laying theblood flow pattern. In this example, we have additionally assumed thatthe start of the injection begins at about the same time as systole(compression of the heart with lower blood flow rates). However, from apractical point of view, timing of the beginning of an injection mayhappen at any time during the heart cycle since it may be difficult tosynchronize injections with the vessel blood flow. As can be seen inFIG. 4D, an injection at a constant V_(i) flow rate (or, as described byQ_(Improved) in FIG. 4C), although notably better than no modulation(e.g., Q_(Agent)) may still result in over-injecting contrast media (attimes) since the blood flow rate (e.g., Q_(Blood)) is less than the rateof injection (e.g., V_(i) or Q_(Improved)). In this case, the areas D inFIG. 4D may indicate such over-injection, where contrast may be injectedinto the aorta (as an example) rather than into the left main artery.

In describing this example further, the arrows in FIGS. 5A and 5Billustrate flows Q_(Blood) (arrow 50) and Q_(Agent) (arrows 52) duringinjection of contrast agent during different phases of the heart cycle.When the injection of contrast medium is greater than the blood flow inthe vessel 24 (FIG. 5A) there will be a tendency for the contrast mediato flow to the least path of resistance. In this case, some of thecontrast media may flow to the aorta 22 and, consequently, systemically.Conversely, when the blood flow (Q_(Blood)) in the vessel is greaterthan the injection flow (Q_(Agent)), the flow of contrast media maypreferentially pass into the vessel 24 (FIG. 5B). In other words, theinjection flow rate (Q_(Agent)) illustrated by arrow 52 in FIG. 5B willfollow the blood flow rate (Q_(Blood)) illustrated by arrow 50.

Various embodiments of the inventive devices and methods will now bedescribed in further detail. Many of these embodiments may control,transform or otherwise modulate a pattern of medium, agent, substance,medicament, or fluidal material delivery to a vessel, vascular bed,organ, or/and other corporeal structures so as optimize the delivery ofmedia to the intended site, while reducing inadvertent introduction (orreflux) of the media to other vessels, vascular beds, organs, and/orother structures, including systemic introduction. Some of theseembodiments may modulate an injection, such as the example shown in FIG.4A, by controlling the flow rate profile of an injection to attain aprofile designed to reduce inefficient agent use (e.g., areas A, Band/or C in exemplary injection profile Q_(Agent) of FIG. 4B), and toobtain an “improved” injection profile Q_(Improved) in FIG. 4C.

Exemplary Modulation Devices and Methods

Some of the “modulators” in the following examples may be located atvarious locations proximate the proximal portion of the therapy system10, as described in FIGS. 3A-3C. For example, a modulation controllingmechanism may be positioned on the injection device outlet, between theinjector 40 and the manifold 38, between the manifold 38 and the guideconnector 28, as well as between the guide connector 28 and the guidecatheter 12. Some other embodiments may also include directlycontrolling the performance of the injection device 40. The placement ofthe modulator may also be highly dependent on the diagnostic,prophylactic or therapeutic procedure to be performed and, as such, thepositioning should not be limited by the examples used herein.

In addition to locations described above, some inventive embodiments offluid modulators may alternatively be positioned in, and/or around,and/or proximate the distal portion of the guide catheter/deliverycatheter 12.

Furthermore, some embodiments of control devices disclosed herein mayadvantageously receive a sensor signal so as to coordinate a valving,controlling, or otherwise modulating function on an injection agentbefore the agent enters an intended target injection site.

One exemplary embodiment of a modulation device 55 is shown in FIG. 6A.Device 55 may be positioned within the exemplary system 10 of FIG. 3C,as shown in FIG. 6C. As such, an “injection” port 56 a of modulator 55has a connector 56 coupled by tubing 42 a to injection device 40, and anoutlet port 58 a of the modulator 55 has a connector 58 coupled bytubing 42 b to manifold 38. FIG. 6A shows the exemplary modulator 55comprising a body 60 having three ports thereon. One of these ports (the“Injection” port 56 a) receives an injection of agent from injectiondevice 40. A “To Guide” port (outlet port 58 a) delivers agent fromdevice 55 to the manifold 38, and subsequently through the guide 12. An“Overflow” port (outlet port 58 b) is activated upon over pressurizationby the injector 40 to the modulator 55, so as to release excessive agentout of the system 10 (i.e., out of device 55).

An example of how such a modulator may function may be determined by theinjection parameters (i.e., pressure, volume, flow rate, etc.) intendedto improve the delivery of the agent. For example, V_(i) of FIG. 4 (withthe exemplary treatment system use as described for and by FIG. 3) maybe approximately 3.0 ml/second. Using various flow equations for flowwithin a conduit (assuming some amount of laminar flow), such as thoseshown in FIG. 7, an injection pressure level (from the injector, forexample) may be derived to provide an agent flow rate delivered from thedistal end of the guide catheter. With a set-up and dimensions asdescribed, a pressure of 75 psi (at or around the proximal portion ofthe guide catheter) may sufficiently produce about 3.0 ml/second ofQ_(Agent) delivered to the distal tip of the guide catheter positionedat the ostium to the left main. This example is intended to beillustrative for the purpose of description and, as such, should not berestrictive or limiting in the scope of the devices and methodsdescribed and disclosed herein. For example, if the treatment device(e.g., balloon catheter 14, stent 16, and wire 18) described above wereto have a different construction (than previously described), such as aproximal and a distal outer dimension of 2.7 F, only 43 psi may benecessary to produce approximately 3.0 ml/second of Q_(Agent).Alternatively, utilizing a guide catheter (e.g., delivery catheter 12)with different inner diameter dimensions might be used in producing amedium flow rate of about 3.0 ml/second, at a lower pressuredifferential. For example, the guide catheter could be larger (0.076inch inner diameter/6.5 F outer diameter) in corporeal areas lesscritical in the performance of the treatment (e.g., descending aorta),while providing advantages of a smaller treatment system (e.g., guidecatheter having 0.70 inch inner diameter/6 F outer diameter) inproximity of the treatment region (for example, 30 centimeters of theguide catheter 12 distal portion). Advantageously, agent flow rate ofapproximately 3.0 ml/second may be accomplished at about 50 psi, whilenot sacrificing the benefit of a smaller treatment system within thecoronary vasculature. In summary, therefore, it is not the intention perse to describe all possibilities of various constructions of treatmentsystems and improvements thereto, but rather it is to provide examplesof how one might construct exemplary devices for use in such exemplarytreatment systems as described herein.

Referring to FIG. 6A, injection of agent from an injection device (asindicated by flow arrow 62) may enter a chamber 64 of modulator body 60having a spring-loaded plunger 66 therein. The plunger 66 in thisexample (and in others to follow) may be in sealing, but sliding,relationship with the chamber 64—such as one might find in a syringe.Compression spring 68 (providing, e.g., spring constant k₁) may bepositioned within the side of the chamber 64 opposing the force ofinjection and configured so as to resist movement of the plunger 66against the force applied by filling the chamber with agent from theinjector. As the agent injection pressure increases in chamber 64, theplunger 66 may move against the compression spring 68. The forcegenerated by the spring 68 against the pressure of injection will bedefined by the spring's spring constant (k) and the distance (L) thespring has been compressed, or otherwise displaced from its equilibrium(Hooke's Law, F=−k*L). FIG. 6A shows a displacement of the spring 68 (atplunger 66) within the chamber 64 of a distance greater than L₁. In thisexample, displacement of the spring/plunger equal to, or greater than,L₁ may allow passage of the pressurized agent to flow through an orificein the chamber 64 and then through the “To Guide” port 58 a at aminimum, threshold pressure (such as indicated by flow arrow 70). In theexample described above, we have hypothetically selected a pressure ofabout 75 psi to produce the intended flow of agent. That is to say, whenthe force within the chamber 64 is equal to 75 psi/(cross-sectional areaof the plunger/chamber), the force derived from the compression of thespring 68 over a distance L₁ should be about equivalent. The spring 68used in producing such a force would have a spring constant (k) tooptimally produce an equivalent force over the displaced length. Thismodulator construction may advantageously produce an injection flowprofile of agent that allows flow to the guide at some intended flowrate that may be radiologically visible (i.e., V_(i)). In our example,V_(i) may be 3.0 ml/second.

Furthermore, as an injection of agent into the modulator 55 is increasedin pressure, the plunger 66 of FIG. 6B may continue compression of thespring 68 along the longitudinal axis of the chamber 64 so as to exposea second orifice in the chamber 64 (e.g., to the “Overflow” port 58 b)at L₂ wherein the highly pressured agent may be diverted away fromintroduction into the guide 12 (such as indicated by flow arrow 72 inFIG. 6B). For example, it may be determined that an acceptable workingrange of a modulator may be 75 psi to 80 psi, to produce controlledinjections with flows in the above example of about 3.0 ml/second toabout 3.1 ml/second. The displacements of the spring 68 with springconstant k₁ at L₁ and L₂ could define these operating pressures/flowrates. An injection greater than 80 psi will result in the excessiveinjection being bled-off into the “Overflow” port 58 b, and notintroduced systemically. Moreover, if the injection should fall below 75psi, no agent will pass into the system (the plunger would be movedwithin the chamber by the spring such that both orifices of the chamberwould close due to insufficient pressure). The exemplary modulatordescribed may advantageously produce an improved injection flow profile,reducing inefficient agent use as illustrated as areas A, B and/or C inexemplary injection Q_(Agent) profile of FIG. 4B, and resembling (withina working range), an “improved” injection profile Q_(Improved) of FIG.4C.

An alternative embodiment of a controlling device 75 may be of theconstruction as shown in FIGS. 8A-8C. In essence, a single chamberdevice such as illustrated in FIG. 6 may be replaced by a double chamberconfiguration so as to provide greater fidelity in the selection ofmodulator working pressures/flow rates.

As shown in FIG. 8A, there may be two separate tanks or chambers withtwo compression springs (having spring constants of K₁ and K₂). Mediumfrom the injection device may be delivered to the device 75 as in device55 of FIG. 6C (as illustrated by flow arrow 62), or any of thealternative locations described herein. Fluid flow from the injectorenters chamber 1 (tank 76) and compresses plunger/spring 78 of chamber 1until an intended pressure (and commensurate flow rate) is obtained.When the intended pressure/flow is obtained (i.e., V_(i) at 75 psi ofthe previous example), the flow of medium passes via an orifice inchamber 1 and out the “To Guide” port 80, as shown in FIG. 8B (such asindicated by flow arrow 82). Chamber 2 (tank 84) is in fluidcommunication with port 80 and may also be pressurized by the injection.Fluid flow from the injector (via port 80) enters chamber 2 andcompresses plunger/spring 86 until another compression level is reachedwithin chamber 2, at which point plunger/spring 86 in chamber 2 willcompress to a point that the passage of fluid is allowed, via an orificein chamber 2, into port 88 (the “Overflow” port). As shown in FIG. 8C,the “decompression” of chamber 2 acts as a “relief valve” and reducesthe pressure of the fluid going to the “To Guide” port 82 if thepressure in chamber 2 exceeds an upper-end threshold (i.e., 80 psi inthe example of FIG. 6). Any additional pressure/volume will be bled-outof the system via port 88 (such as indicated by flow arrow 90 in FIG.8C) and not introduced through the guide. In operation, the use of adevice such as device 75 with an agent injection system may likewiseproduce an “improved” injection agent flow profile, reducing inefficientagent use as illustrated as areas A, B and/or C in exemplary injectionprofile Q_(Agent) of FIG. 4B, and resembling (within a working range)the “improved” injection profile Q_(Improved) of FIG. 4C.

Advantageously, an alternative modulator design, as shown in FIGS.9A-9C, might also accommodate cessation of injection from the injectiondevice without fully ceasing the injection of medium to the guide. Forexample in a modulator 95 having two chambers or tanks 96 and 98 such asshown in FIG. 9A, tank 2 might include a compression spring with a lowerspring constant than the compression spring in tank 1, but allow morefilling of the tank 2 (i.e., greater compression length of its spring),while providing flow to the guide at an intended rate. In essence, tank2 might act as a “holding tank” of the injection.

In further viewing FIG. 9A, the modulator 95 may comprise two tanks 96and 98 with two compression springs 100 and 102 (with spring constantsof K₁ and K₂ respectively). Medium from the injection device may bedelivered to the device as in the device of FIG. 6B (as againillustrated by flow arrow 62), or any of the alternative locationsdescribed. Fluid flow from the injector enters chamber 1 and compressesplunger and spring 100 of chamber 1 until an intended pressure (andcommensurate flow) is obtained. When the intended pressure/flow rate isobtained, the flow of medium passes out of chamber 1 via an orifice andinto chamber 2 via channel 104, and then out the “To Guide” port 106, asshown in FIG. 9B (as illustrated by flow arrow 108 in FIG. 9B). Inessence, chamber 1 provides chamber 2 with a pressurized flow of a valueequal to, or greater than, some intended limit (i.e., a minimumthreshold, such as 75 psi). If chamber 2 should pressurize with fluidgreater than an upper threshold of some working pressure (for example,80 psi) spring 102 of chamber 2 may compress to a point to allow passageof fluid out of chamber 2 via another orifice and into port 110 (the“Overflow” port) with any additional pressure/volume bled-out of thesystem, and not introduced through the guide (as illustrated by flowarrow 112 in FIG. 9B). Again, an injection system equipped with a devicesuch as device 95 may aid in producing an “improved” agent injectionprofile similar to profile Q_(Improved) in FIG. 4C.

Although the previous example describes using device 95 assimultaneously injecting a medium while delivering the medium to/throughthe guide catheter, the device 95 may also be employed to deliver themedium in a “sequential” fashion. For example, to “sequentially” injecta medium (i.e., fill a chamber with a medium to be delivered, but allowtime before release of the injection), or avoid an interruption in thedelivery of a medium, the device 95 of FIG. 9C may advantageouslycontinue to deliver medium to the “To Guide” port 106 as spring 102decompresses. As shown, the cessation of the injection 62 at a minimumlevel (as illustrated at 113 in FIG. 9C) may result in the cessation ofmedium delivered via channel 104 from chamber 1 (as illustrated at 114in FIG. 9C) to chamber 2 since spring 100 has sufficiently decompressedso as to occlude the orifice in chamber 1 into channel 104, thusstopping the flow of medium from chamber 1 to chamber 2.

In this example, tank 2 may “bleed-out” the medium contained within tank2 while no additional medium is injected into the device 95. The device95 of FIGS. 9A-9C might also have a “relief” mechanism or one-wayvalving type system (such as valve 107 in FIG. 9C) attached to the “ToGuide” port to assure that a minimum pressure is maintained as chamber 2decompresses (i.e., a relief valve that only operates above the intendedpressure of, say 75 psi and only allows flow to the guide if minimumpressure is maintained). Conversely, the spring of chamber 2 may also bedesigned to “close” the orifice to the “To Guide” port if a minimumlevel of pressure is not maintained. FIGS. 9A-9C also illustrateknurled-knob bolts 100 a and 102 a threadably extending from tanks 1 and2, and attached to springs 100 and 102, so as to provide a mechanism forindependently adjusting the forces delivered by their respectiveplungers.

An alternative example of a regulator that could be used for sequentialor/and simultaneous injection may be seen in FIGS. 10A and 10B. In thisexemplary embodiment, a pressure chamber is filled with a quantity ofmedium to be delivered. The pressure and volume of the medium to beinjected to a guide may be determined when it is introduced into thechamber, or conversely the chamber may be designed to provide/applypressure upon the medium within the chamber after its introduction.FIGS. 10A and 10B illustrates such a modulator 115 that comprises acompartment (medium chamber 116) defined for a medium to be injected,another compartment (gaseous chamber 118) for receiving a gaseous medium(e.g., air), and a deformable bladder 120 sealingly separating thecompartments 116 and 118. As seen in the example, a valve 122 may beused to facilitate the flow of gas in and out of compartment 118 (e.g.,to seal the gaseous compartment 118). The medium to be delivered can beintroduced into the chamber 116 of the modulator 115 with the gaseouscompartment valve 122 closed. During introduction of medium, the startof which is shown in FIG. 10A (fluid filling from the injector asindicated by flow arrow 62), the bladder 120 may deform into the gaseouscompartment 118 until the medium obtains an intended pressure for thedelivery of the medium to the guide catheter. Not shown in FIG. 10 arethe valve mechanisms (such as those found on the manifold 38, forexample, of FIG. 3C) to allow the passage of medium, and retention ofmedium within the modulator 115, until an injection to the guide iswarranted. The medium may be released from the chamber 116 by opening,or otherwise activating, a valve (not shown) between the medium chamber116 and the guide. FIG. 10B illustrates releasing of the medium from thechamber 116 to the guide catheter (as indicated by flow arrow 124).

Conversely, the chamber 116 of FIG. 10A might be filled with injectionmedium first; and, then pressurized to an intended delivery pressure byintroduction of gas into the gaseous compartment 118, thus applyingpressure to the medium through the bladder 120.

Although the previous description of device 115 may be illustrated as“sequential” delivery, device 115 may be designed to act as a“capacitor” during simultaneous delivery. In this case, there may beanother port (a “To Guide” port configured on the medium chamber 116,not shown), to allow delivery from the device 115 during injection.

A modulator 115, such as example devices of FIGS. 10A and 10B, mayadvantageously provide a flow profile that resembles the injectionQ_(Improved) of FIG. 4C, at least as it pertains to areas A and C ofFIG. 4B, since the injection may be delivered quickly to a V_(i) flowrate, accommodating a quick ramp up and a fairly even flow rate for ashort period of time. With respect to area B of FIG. 4B, chamber 116 ofFIGS. 10A and 10B may decompress (while delivering flow) to a level thatis below an “improved” working range. To compensate for this, amechanism (such as a one-way value; e.g., valve 117 in FIG. 10B) may bedisposed between the chamber and the guide to assure that the mediumflow rate delivered meets the intended limits (e.g., minimal flow rate)for the injection, or terminates the flow.

An alternative construction of a modulator may include a chamberconstructed with a constant force spring, as shown in FIGS. 11A and 11B.Such a spring, by design, may deliver a constant force on a member (suchas a plunger) over its working range (displacement). A modulator 125 ofthis type may include a conical spring (126 as shown in FIG. 11A) as anexample of such a spring that can be made to have a constant forcedelivered over different compression lengths (displacements fromequilibrium). The spring 126 may have variable pitches, with a largerpitch in its larger outer coils and a smaller pitch in its smaller innercoils, thus collapsing/expanding the coils at the same force duringcompression/decompression. Similar to the other devices describedherein, the alteration of an injection's pressure and flow may beperformed while delivering media to a delivery site, as well asperformed by more than one step/sequence in delivery.

Using such a constant force injection modulator 125 as described, onemight inject a quantity of medium into a chamber 128 of modulator 125(as indicated by flow arrow 62), leading to compression of conicalspring 126, as seen in FIG. 11B. Once a desired volume of medium has bereceived within chamber 128, injection may be stopped and/or back flowof medium from chamber 128 to the injector prevented (such as bymanipulation of a valve—not shown), as further illustrated at 129 inFIG. 11B. Upon actuation, or otherwise release, of medium from thechamber 128 (such as opening of a valve to the guide—not shown) aplunger 130 may drive (as urged by compressed spring 126) the mediumfrom the chamber 128 with constant pressure (and commensurate volumeflow rate) toward the guide via an orifice in chamber 128 leading to the“To Guide” port 132. It might be advantageous with this modulatingsystem 125 to allow “space” within the chamber 128 for the plunger 130to close the “To Guide” orifice once a desired volume has beendelivered.

An alternative construction (not shown) for the modulation system 125 ofFIGS. 11A and 11B might also include mechanically driving adisplacement/plunger element at a constant force within/upon a chamberso as to achieve a constant pressure upon the chamber and drive agent ata constant flow rate to the delivery catheter. Such a chamber might havea construction as shown in FIG. 11A. An alternative embodiment forsimply providing constant force on a plunger in a chamber might includethe placement of a weight upon a vertically-mounted plunger elementwithin the chamber. For example, a syringe-type chamber might bevertically situated with the displacement actuator/element located above(further away from the center of the earth), and the outlet port locatedbelow (closer to the center of the earth). After filling the chamberwith medium, various weights may be placed upon the displacement elementso as to create the intended constant force upon the plunger (e.g.,using gravity upon a mass in deriving a constant force). When aninjection is needed, the medium may be released (or otherwise actuatedto be released) from the chamber by opening a valve (such as astopcock). The opening of the valve thus allows the medium to exit thechamber as a result of the force placed on the medium from the weightupon the plunger. The measure of the weight might be, for example,similar to the force determined for the constant force modulator 125described above.

An alternative use of regulator 125 of FIG. 11 might be employing theregulator during the simultaneous injection and delivery of mediumto/through the delivery catheter. With this application, injectingmedium into chamber 128 with constant force spring 126 may provide a“pre-loaded” resistance to filling of the chamber. Once a pre-set levelof pressure is achieved, regulator 125 may allow injectate to pass intochamber 128 and out of the chamber through the “To Guide” port 132.Additional filling of chamber 128 may take place during injection ofmedium if the injection pressure is greater than the pre-set springresistance (and assuming sufficient resistance to delivery in thedelivery catheter). In addition to filling, the chamber 128 may“discharge” medium (a reduction in volume) at a constant pressure(approximately the pre-set level of pressure) if/when the pressure fromthe injector is less than the pre-set resistance by constant forcespring 126. With this exemplary simultaneous modulation, regulator 125may act as a “capacitor” (i.e., having the ability to store anddischarge a pressurized volume of medium) so as to “level-out” or“smooth-out” the pressure/flow profile of a medium directed to thecatheter during injection.

Further to the description of modulator 125, and other media modulatorsdescribed herein, manual injection (such as a syringe) during deliverymedia to an injection site might have varied pressures/flows passing tothe modulator. Not only might the flows/pressures to the modulator bevaried, but it is conceivable (depending on the system construction)that the flow of injection medium might, at times, return into theinjector (syringe). As an example, it is possible that an administratorof a syringe might release the pressure placed upon the plunger.Depending on this reduced force, it is possible that the pressure/fluidstored into chamber 128 may be diverted back to the syringe—a functionof the “least path of resistance” to the flow from the capacitancechamber 128.

Advantageously, a modulator having a constant force chamber of suchconstruction may be configured to improve a medium injectionflow/pressure profile delivered to a delivery catheter. FIGS. 20 to 22illustrate such an alternative system configuration/construction, andits method of use, which may provide an improved pressure/flow deliveryprofile. A modulator system 325 of FIG. 20 includes a manifold 326having several elements attached to the manifold 326 to include: areservoir or vial 328 of medium (i.e., contrast agent), a constant forcechamber 330, an injector 332 (e.g., syringe), a delivery catheter 334,and a 4-way stopcock 336. These elements may be configured so as to bein fluid communication with one another, at times, via suitable tubularmembers T. Valves A (manifold to catheter), B (medium vial to manifold),C (constant force chamber to manifold), and D (injector to manifold) mayallow for opening and closing such fluid communications between themanifold 326 and different elements of 328, 330 332, 334 and 336 ofmodulator 325. Note that 4-way stopcock 336 may provide the valvingfunctions of valves C and D in lieu of separate valves/attachments. Offurther note, the constant force chamber 330 may be configured, asillustrated, to accommodate a weighted force element (discussedpreviously) or a coiled constant force element, so as to deliver aconstant force upon medium in a chamber therein with a displaceableplunger or surface. These are but two examples of how one mightconfigure a constant force chamber and, as such, are to be illustrativebut not limiting in the various configurations to construct a constantforce apparatus.

In the exemplary method of performing an injection modulation, contrastagent from vial 328 is drawn into the syringe 332 by closing valve A (toprevent flow between the manifold 326 and the delivery catheter 334),opening valve B (to permit flow between the medium vial and the manifold326), closing valve C (to prevent flow between from the constant forcechamber 330 and the manifold 326), and opening valve D (to permit flowbetween the manifold 326 and the syringe 332), as represented in FIG.21. The syringe 332 may be filled with injectate medium by drawing on aplunger 338 of the syringe 332, as represented in FIG. 21 by arrow 339,to thus draw medium from vial 328 into syringe 332. Valve B (betweenmedium vial 328 and manifold 326) may be closed when sufficient mediumhas been drawn into syringe 332.

Whether a construction having a weighted force element acting upon aplunger (such as illustrated by weight system 330 a), a constructionemploying a constant force spring acting on a plunger (such asillustrated by constant spring force 330 b), or an alternative constantforce contrivance, a load is determined to be deployed upon the constantforce chamber 330 (and its fluid contents) sufficient in regulatingmedium flow to be delivered by the delivery catheter 334. For the sakeof elucidation only, say a pressure of 50 psi is wanted at the manifold326 (e.g., into the proximal port of the delivery catheter 334) tocreate an improved medium delivery flow through the catheter 334.Constant force chamber 330 may be configured so as to generateapproximately 50 psi upon a fluid within, entering, or exiting, theconstant force chamber 330 when valve C is opened (i.e., open to permitflow from constant force chamber 330 into the modular system 325).

When an injection of medium to an injection site is warranted, valves A(to catheter 334), C (to chamber 330) and D (to syringe 332) may beopened and the plunger 338 of the syringe 332 depressed (in direction ofarrow 340 in FIG. 22). As the plunger 338 of the syringe 332 is quicklydepressed, the fluid ejected from the syringe 332 will want to traveltowards the least path of resistance, simultaneously driving fluid tothe catheter 334 (as represented in FIG. 22 by medium flow arrows 342)while passing into the constant force chamber 330. Rapid introduction ofmedium by the syringe 332 will allow the pressure within the manifoldapparatus to quickly obtain 50 psi, and allow for filling the constantchamber force 330 with medium (via flow of arrow 344) when pressure isgreater than 50 psi. Thus, constant force chamber 330 acts as acapacitor as it takes on more medium at, or above, a pressure ofapproximately 50 psi; while, also allowing the delivery of medium to thecatheter 334 at approximately 50 psi (via flow arrows 342). In essence,the flow delivery profile of the modulator 325 may reduce the “wasted”contrast due to ramping-up pressure/flow (area A of FIG. 4B); as wellas, reduce the “wasted” contrast from over-injecting into the deliverycatheter (area C of FIG. 4B) by maintaining a more constant pressurewithin the manifold.

In the example shown in FIGS. 20 to 22, once the operator has filled theconstant force chamber 330 with contrast medium to some degree, theconstant force chamber 330 may continue to discharge the wanted 50 psito the delivery catheter 334 even if the injection flow is diminished,thus facilitating a “smooth” injection to the delivery catheter 334.

When it is determined that sufficient medium has been delivered by thesyringe 332, releasing the plunger 338 (e.g., allowing the plunger 338on the syringe 332 to negatively displace with no loading) may allow arapid drop-off of pressure from the manifold 326 as the pressure withinthe constant force chamber 330 may be dissipated by discharging flowaway from the delivery catheter 334 and into the syringe 332 (e.g.,least path of resistance—represented by the phantom arrows 346 in FIG.22). Thus, the rapid decrease in pressure delivered to the deliverycatheter 334 may act to reduce the “wasted” contrast as typically seenat the tail end of an injection (e.g., area B of FIG. 4B). It is alsopossible to facilitate the rapid termination of the injection by closingvalve A (manifold to catheter) before, during, or quickly after aninjection is terminated by the syringe 332. The termination of themedium injection also may be enhanced by including other mechanisms(such as a one-way valve) so as to quickly shut-off delivery to thecatheter 334 when there is insufficient pressure (e.g., when a selectedlow pressure threshold is reached). Such a one-way valve could be placedat various locations within the modulator system 325, including itsresiding between the manifold 326 and the delivery catheter 334, alongthe tubular connector therebetween, such as illustrated by valve 317 inFIG. 22.

Depending upon the circumstances, it may be desired to change, fromprocedure to procedure (or even during a single procedure), the loadprovided by the constant force chamber 330. When the constant forcechamber 330 is configured to accommodate a weighted force element (suchas weight system 330 a), this may be accomplished by changing the amountof weight being applied to the plunger. When the constant force chamberis configured as a coiled constant force element (such as illustrated byconstant spring force 330 b), the load may be modified by changing thecoiled constant spring element. However, these approaches may becumbersome and require a stockpile of alternate components (e.g., setsof weights or springs) to achieve varied loads. A constant force elementthat may be varied (e.g., the ability to change the constant forcedelivered) with a platform capable of varying the constant force, suchas 402, may be of value.

As illustrated in FIG. 26, a variable force delivery platform 402 foruse in a modulation system such as modulation system 325 is provided toact upon a plunger 404 which in turn presents a load to the medium via aforce surface within a plunger chamber 406 filled with medium. Thechamber 406 thus may act as the pressure chamber within the constantforce chamber 330 (such as illustrated in FIG. 22) that may be connectedby tubular member T to valve C on stopcock 336.

The platform 402 may include a constant force spring 408, such as thecoiled constant spring element illustrated in FIG. 26, which is operablyconnected at a free end 410 of the spring 408 to a first end 412 of apivotable lever 414. A portion of the lever 414, adjacent a second end416 thereof, may be operably engaged with a free end 418 of the plunger404. The spring 408 may be coupled to the lever 414 so as to provide aconstant spring force, such as illustrated by force arrow 420, upon thelever 414 adjacent its first end 412.

The lever 414 may be pivotally coupled to a housing or other supportstructure as at pivot point 425 in FIG. 26. Thus, the lever 414 maypivot about point 425 due to the application of force 420 adjacent itsfirst end 412 and a corresponding, yet opposite, force 430 beingimparted adjacent the second end 416 of the lever 414. The force 430 maybe applied via the lever 414 and plunger 404 to the medium in thechamber 406, and is defined by the spring force of the spring 408 as itis transferred via the lever 414 to the plunger 404. The force transferis dependent upon the pivoting of the lever 414 about its pivot point425.

The amount of constant force thus applied to the medium in the chamber406 can be modified by changing the position of the pivot point 425relative to the lever 414. In other words, by moving the pivot point 425toward or away from the spring 408, the effective pivotable length ofthe lever 414 between the spring 408 and pivot point 425 is changed. Theamount of force 420 applied to the lever adjacent its first end 412 doesnot change, but movement of the pivot point 425 will alter the amount offorce 430 applied at the second end 416 of the lever 414.

This lever and pivot point arrangement is schematically illustrated inFIG. 26 as a fulcrum 442, which as illustrated, is mounted on suitablesupporting structure of the constant force chamber 330. Leaving allother things equal, movement of the fulcrum 442 and its associated pivotpoint (e.g., from left to right and vice versa, as seen in FIG. 26) willchange the force 430 relative to the plunger 404. This optionaldirectional movement of the fulcrum 442 is illustrated by arrow 444 inFIG. 26. When the fulcrum 442 is moved toward the first end 412 of thelever 414, the effective lever arm distance between the spring 408 andthe pivot point 425 is shortened, thus lowering the force 430 applied tothe plunger 404. Alternatively, when the fulcrum 442 is moved away fromthe spring 408 (and toward the second end 416 of the lever 414), theeffective lever arm distance between the spring 408 and pivot point 425is lengthened, resulting in a greater force 430 applied to the plunger404. Accordingly, the constant force applied to the medium in thechamber 406 can be changed simply by changing the location of the pivotpoint 425 relative to the length of the lever 414, and in this example,that is accomplished by movement of the fulcrum 442 along its possibletravel movement trail represented by arrow 444. Advantageously, this mayallow for incremental adjustment of the constant force applied to themedium in the chamber 406.

In one example, the position of the fulcrum 442 is determined byplacement of a “pin” along a “pin slot” having a discrete number of pinlocations. Each pin location relative to the pivoting lever 414 therebydefines the fulcrum 442 position, which in turn defines apre-established load to be placed on the medium in the medium chamber406 depending upon the force of the constant force spring 408. Anexemplary pin location slot 450 is illustrated at FIGS. 27 and 28. Theslot 450 may be further defined by a connected line of circular pinreceiving holes 452 (illustrated in FIG. 27 as “pin receiving holes” 452a to 452 s, as viewed from left to right). The desired constant force isselected by inserting a pin (such as shown as pin 454 in FIG. 28) into aselected pin receiving hole 452 of the slot 450. The amount of forcethat will be applied to the plunger 404 may be determined by which pinreceiving hole is selected. Selecting a pin receiving hole adjacent afirst end 456 of the slot 450 will result in less force being applied tothe plunger 404, while selecting a pin receiving hole at a second end458 of the slot 450 will result in a greater force being applied to theplunger 404. By way of example, in a left main coronary artery setting,for effective medium modulation, less force will be required when alarger guide catheter is deployed. For a six French or a seven Frenchguide catheter, placing the pin 454 in the pin receiving hole 452 s mayprovide sufficient constant force on the medium in chamber 406 todeliver a medium at a desired rate. However, when a seven French guidecatheter is used with a treatment (“Rx”) catheter, more constant forcemay be required to deliver a medium, and thus the most appropriatelocation for the pin 454 is in pin hole 452 r. In a further example, ifa five French catheter is being deployed which includes a “Rx” catheter,the pin 454 may be placed in pin hole 452 a to provide a greaterconstant force for the medium being supplied by the constant forcechamber 330 into the modulator system 325.

Other exemplary constant force “pin” settings for use with differentcatheter configurations may be seen in FIG. 27. The settings shown areexemplary of a situation wherein one might expect approximately 2 ml/secof medium delivered with a constant force chamber 330 of approximately50 psi, as an example. In the context of the example of FIG. 27, theseterms may generally mean as follows: “Guide” means a coronary guidecatheter, “Diag.” means a coronary diagnostic catheter, “Rx” means acoronary treatment catheter, and “OTW” means an over-the-wire coronarytreatment catheter.

An exemplary constant force chamber 330 having the slot 450 and itsassociated pin 454 for manipulating the fulcrum 442, and its associatedpivot point 425, is illustrated in FIG. 28. Other arrangements formoving the fulcrum 442 along or about lever 414 and defining theirrelative positions are also contemplated, such as rack and pinionmovement, magnetic couplings, and other like contrivances that mayprovide the ability to vary a constant force delivered to a pressurechamber 406 thru plunger 404.

FIG. 29 illustrates an alternate variable force delivery platform 502,where instead of a constant spring 408, a weight system 508 is employedto define a constant force such as illustrated by force arrow 520. Theforce from the weight system 508 is transferred to the lever 514 at 510by suitable means, such as a cable and pulley arrangement as shown.Other than the source of the constant force being a weight systeminstead of a constant spring, the platform 502 operates in a similarmatter to the platform 402 described above. Like elements and featuresare shown in FIG. 29, indexed upwardly by 100 using reference numeralssimilar to those illustrated in FIG. 26.

An alternative embodiment in the modulation of flow through a device tocontrol injections may be found in FIGS. 12A and 12B, which illustrate aconstant flow rate modulator 135 that may advantageously modulate theflow rate delivered to the guide (or any other delivery device), versusthe constant force of modulator system 325. A modulator such as thismight be useful for delivering a constant flow rate of a medium to atarget site, independent of using different conduit configurations. Forexample, the resistance to flow of a medium through an angiographiccatheter (for diagnostic visualization of an artery) may be differentthan the treatment system described previously. And, as such, thepressure required to drive constant agent flow through an angiographiccatheter typically may be lower than the pressure necessary to drivesimilar agent flow through the treatment system. Advantageously, aphysician may be able to perform an angiographic assessment (with anangiographic catheter) of an artery, as well as a treatment (with atreatment system) with the same modulator delivering similar constantflows of agent. An arrangement as shown in FIGS. 12A and 12B may allow aphysician to switch between both agent delivery systems with the samemodulator 135. This is in comparison to say, the constant force ofmodulator system 325, wherein the weight, the constant force coil, orthe constant force contrivance may require adjustment of the force toaccommodate different system considerations (e.g., guide catheter,treatment catheter, etc.).

Referring to FIG. 12A, the injection device provides an injection (seeflow arrow 62) into a chamber 136 of the modulator 135. The injectionacts upon plunger 138 (that is sealably and movably disposed withinchamber 136, and biased in opposition to initial injection mediumpressure by variable force spring 139) with a force derived from thepressure of the medium over the area of the plunger 138. The flow ofmedium is directed out of chamber 136 along an injection flow path 140,by-passing the plunger 138, and then re-establishing flow within thechamber 136, via an orifice 142, on the guide side of the plunger 138.Depending on the pressure that the medium experiences on the guide sideof the modulator 135, the spring-engaged plunger 138 will be driven (bythe force of that pressure) to a location along the orifice 142 passingthrough the wall of the chamber 136. The placement of the plunger 138(and its associated spring 139, and the bias force of spring 139) andits relationship to the orifice 142 may partially restrict the flow ofthe medium into the guide portion (i.e., guide catheter side) of thechamber 136. As an example, the orifice is held completely open in thedrawing of FIG. 12A, suggesting the pressure of the injection may benearly the pressure in the guide portion of the chamber 136, with themodulator “opening the flow” of the orifice 142 as much as possible toallow greater flow. The differential of pressure, and thus the forcesacting upon both sides of the plunger may be nearly the same in FIG.12A. An example of this scenario may be when there is relatively highresistance to medium flow in the delivery guide (e.g., when in use witha treatment system).

Conversely, FIG. 12B shows the orifice 142 partially occluding the flowfrom the injection flow path 140 into the guide portion of the chamber136. In this case, there may be less resistance (i.e., medium flows morereadily) from the guide or delivery catheter and the differential inpressures within the two sides of the chamber 136 have increased. Inother words, the injection path has been restricted (driven by thepressure differentials) to drive the fluid in a delivery catheter havingless resistance (and, therefore requiring less pressure) in deliveringan equivalent flow rate (such as when in use with an angiographiccatheter). In both cases presented, the flow rate of medium to/thoughthe delivery catheter may be the same; however, it is the modulator thatmay be configured to adapt/change resistance to flow in order toaccommodate constant flows (delivery of medium with different systemicresistances).

The example of the flow modulator of FIGS. 12A and 12B illustrates achamber with a single, graduated orifice in performing the constant flowrate modulation function. However, such a function could be performedwith a multitude of orifices, as well as with different cross-sectionalareas of the orifice(s) to accomplish the same intended function. Inaddition, other forms of variable pressure restrictors (having constantflow rate modulation) may accomplish the intended function. As such,these alternatives are considered within the scope of the discloseddevices and processes.

It should be also noted that the exemplary descriptions have assumedthat the ancillary tubings/connections/channels within and/or betweensystem components/devices, are relatively large and may have negligible“resistive” impact on the overall flows/pressures modulated by thedevices. For example, the pressure drop created by the lumen of thechannel between chambers 1 and 2 of FIGS. 9A-9C, or within theconnective tubings and/or connectors of FIGS. 6A-6C should be minimal.If not, design changes could be made to accommodate for the additionalresistances created with such connections without deviating from thescope of the disclosed devices and processes.

Although the various constructions of modulating devices have beendescribed as having chambers with springs therein, it is clear that anypassive and/or active biasing or valving mechanisms (or any combinationthereof) might also be used to produce similar functions, includingapparatuses being significantly smaller than the devices illustrated.For example, hydraulic valves, release valves, one-way valves mayperform functions so as to activate or otherwise modulate flow (i.e.,allow flow) upon a known/determined flow rate and/or pressure, as wellas deactivate (stop or limit flow) once a known/determined flow rateand/or pressure condition has been obtained. Furthermore, passivedevices such as fluid flow restrictions (i.e., tubular members) and/ordiffusers may also be utilized in modulating the flow. These restrictivedevices may not necessarily define an “on-off” (e.g., digitally “thereis” or “there isn't” flow based on pressure) restriction, but rather actto affect the flow rate in the catheter based on restrictions to flow inthe total system. It is within the scope of the devices and methodsdescribed herein to include such alternative devices, or devices incombination, to produce similar injection modulation effects.

As an example of passive devices that may alter, or modify, the flow offluid delivered through a catheter, a review of the resistance to flowof the embodiment in FIG. 6 may be seen in FIG. 51A (noting that Q=ΔP/R;where Q=fluid flow through a system, ΔP=pressure differential across thesystems and R=Resistance to fluid flow in the system; see e.g., FIG. 7).In the example shown in FIG. 51A, an injection from a syringe passesinto a chamber 64 with pressure P_(I) and flow Q_(I). There is initiallyresistance to flow (R₁ of the modulator device 55 “valve”) in thechamber 64 from the spring constant k₁ of the spring 68. Once theresistance is overcome (say, for example, by injecting over 30 psi),flow is allowed to pass to the catheter through orifice 58 a (“ToGuide”), at a pressure of P₂ and flow of Q₂. This pressure/flow might beconsidered a minimum threshold of delivering flow to the cathetersystem. Upon increased pressurization from the injection (e.g., fromP_(I)), additional resistance R₂ to flow will be created by the spring68 in the modulator device 55 (in addition to the resistance R_(c) ofthe catheter/system). Once resistance R₂ is overcome through increasedpressurization/flow (say, for example, 50 psi), fluid flow will beallowed to flow out of the “overflow” orifice 58 b (see, e.g., FIG. 6B)at a pressure of P_(o) and flow of Q_(o). This might be considered amaximum threshold of pressure at which the medium may be injected intothe guide (e.g., any pressurization above this will result in bleedingor diverting medium out of the system). It should be noted that when thepressure at P₂, for example, is high enough to allow flow (e.g., minimumthreshold) to the guide, but less than the amount of pressure toovercome R₂ (e.g., maximum threshold), the flow of fluid to guide (andout of the catheter) will vary as a result of the pressure. As well as,when the pressurization exceeds the pressure at which the resistance ofR₂ has been overcome, overflow Q_(o) from the system will continue toincrease with pressurization. As shown in FIG. 51A, the flow exits thecatheter system at a pressure P_(e) and a flow of Q_(c).

Looking at FIG. 51A, it is possible to alter the flow delivered to thecatheter (or guide) system without using the resistance of R₁ (derivedfrom the valve from the modulator device 55). The flow diagram of thisexample may be seen in FIG. 51B, wherein the pressure (P_(I)) and flow(Q_(I)) may be directly delivered to the catheter and an overflow path,in parallel. In this example, Q_(I) may be split (based on differentresistances between the two parallel pathways depending on the amount offlow one might want to direct to the catheter system. As an example, ifa flow rate of 3 ml/sec were the maximum one wanted to deliver to thecatheter, and the catheter system had a resistance of R_(C) and possiblemaximum pressure and flow of (i.e., depending on the syringe, individualstrength of the operator, convenience, etc.) P_(I) of about 60 psi andQ_(I) of about 5 ml/sec, one could design the constant resistance R_(O)of the overflow, or diverting, fluid pathway (e.g., tubular member) toallow 3 ml/sec delivered to the guide at about 60 psi P_(I). Thisembodiment allows for a simple solution for diverting flow, whilemodifying the delivered medium, so as not to exceed some approximateinjection threshold amount that results in excess contrast beingdelivered. It should be noted in this configuration that there would bea constant “bleeding” off of the injection, irrespective of theinjection pressure. Moreover, it is also possible the resistance of the“overflow” (R_(O)) may be created by alternative constructs, such as:resistance as a result of a tubular diameter or length dimension;resistance created by flowing through a restrictor, resistor, diffuser,filter medium, etc.; resistance created by alteration in the normalfluid path (pinching of the line in a discrete fashion); resistancecreated by a combination of any, or all, of the above (for example). Tothis end, overflow resistance R_(O) of the above example could simply bea “tube” having sufficient resistance (e.g., diameter/length), or theplacement of a resistance, such as a narrowing in a tube (e.g.,pinching) to establish sufficient resistance.

An alternative embodiment of diverting flow can be seen in FIG. 51C.FIG. 51C illustrates a flow pattern wherein the initial flow of Q_(I) isdirectly injected to the catheter system, and upon reaching a minimumpressure (e.g., a pressure P_(I) and associated flow rate Q_(I)), a“check valve” may be employed to start diverting the fluid away from thecatheter system. In this case, the check valve resistance (R_(CV)) is inaddition to, and prior, to the arrangement illustrated in the overflowtubing resistance (R_(O)). In FIG. 51C, the fluid pressure and flow rateexiting the check valve are represented as P_(CV) and Q_(CV). Oneadvantage of this configuration (versus the arrangement illustrated inFIG. 51B) is that this configuration may allow less fluid to bedischarged, since it diverts at a higher pressure point. FIG. 30 showsan exemplary device capable of producing the fluid flows as described.

As has been described, one means for producing an operative medium flowrate is to “strip off,” “bleed off,” or otherwise divert some of themedium flow coming from the syringe away from the catheter system. FIGS.30 and 31 illustrate one exemplary arrangement for doing so. In thisarrangement, syringe 332 may be fluidly coupled to medium reservoir 328by suitable tubular members T₁, T₂ and T₃, and via manifold 326. Foruse, syringe 332 may be loaded with medium from medium reservoir 328 andthen valve B on manifold 326 is manipulated to prohibit the flow ofmedium back to reservoir 328 via tubular member T₁.

A flow diverter assembly 550 may be positioned in the medium flow pathbetween the syringe 332 and the catheter 334. As can be seen in FIG. 30the flow diverter assembly 550 may be coupled to a four way stopcock 552allowing the assembly 550 to be selectively active or inactive in theflow of the medium, if desired. For example, when the syringe 332 isbeing loaded with medium from the medium reservoir 328, the stopcock 552may be positioned to permit medium flow between tubular members T₂ andT₃, but not to tubular member T₄ (disposed between the stopcock 552 andthe flow diverter assembly 550). When the stopcock 552 is positioned toallow flow into tubular member T₄, medium flow may pass into the flowdiverter assembly 550 upon pressurization from the syringe 332. Like theexemplary agent flow schematic in FIG. 51C, the flow diverter assembly550 includes a check valve 554 aligned to prevent the flow of mediuminto the flow diverter assembly 550 until a certain medium pressurethreshold is reached (e.g., 20 psi). Once the threshold pressured isexceeded, the check valve 554 may permit fluid flow into the flowdiverter assembly 550. After traversing check valve 554, medium flow maypass distally therefrom via tubular member T₅ to a medium reservoir,which may be reservoir 328, as shown. When the pressure of the mediumreaching the check valve 554 from the syringe 332 is lower than thethreshold pressure, the check valve 554 seats itself so as to preventback flow (i.e., medium flow out of the flow diverter assembly 550 viatubular member T₄).

In one embodiment, the flow diverter assembly 550, upon reaching athreshold pressure, may divert approximately 40% of the medium flow fromthe syringe 332, thereby allowing 60% of that flow to reach the catheter334. For example, upon reaching a threshold pressure delivered to checkvalve 554 of flow diverter assembly 550 from syringe 332, the flow ratedelivered from the syringe 332 could be 5 ml/sec.; however, the desiredflow rate to the catheter 334 at this pressure may be 3 ml/second. Inthis case, flow diverter assembly 550 may be designed (i.e., length,diameter, configuration or other restrictive type structures) so as toallow a medium flow rate of 2 ml/sec. to “bleed off” (or, otherwise bediverted through tube T₅) from the total amount of medium delivered tothe catheter 334. In one regard, this flow diversion arrangement can beconsidered to form flow resistors disposed in parallel, with one form ofresistor being the catheter 334 itself, and the other form of resistorbeing the flow diverter assembly 550 (see again, e.g., FIG. 51C.). Itshould be noted that a change in the “catheter resistance” (e.g., changein the delivery catheter system) may require changing the resistancesimposed by flow diverter assembly 550 to achieve similar diversion offlow (e.g., 2 ml/second).

In one embodiment, the flow diverter assembly 550 may include amechanism that allows for selection and changing of a level of flowresistance and/or variation in the amount of medium flow allowed throughthe flow diverter assembly 550. Advantageously, a variable flow diverterassembly 550 which is capable of changing resistance may allow a user toswitch medium delivery systems (i.e., a diagnostic catheter to a guidecatheter with a treatment device) without having to change-out orreplace the flow diverter assembly 550. In an exemplary embodiment,changing the level of flow resistance of the fluid medium through theflow diverter assembly 550 comprises changing an effective size of atleast a portion of the fluid medium flow path through the flow diverterassembly 550. In simplified form, FIG. 31 illustrates a switch plate 560that is movable between three positions relative to a base 562 of theflow diverter assembly 550 to allow for manual selection of a level offlow resistance of the fluid medium through the flow diverter assembly550 to provide greater medium fluid flow resistance with higher pressureof injection. The switch plate 560 has an elongated opening 563 thereinthat may be sized to receive flexible and deformable tubular member T₅therethrough. As illustrated in FIG. 31, the opening 563 may be largerin a first area 564, with a diminished dimension in at least one otherdirection 565 in a second area 566, and with a further diminisheddimension in at least one other direction 567 in a third area 568. Thetubular member T₅ extending out of the flow diverter assembly 550 andtoward the reservoir 328 may extend through opening 563 on the switchplate 560. The switch plate 560 may be movable relative to the base 562in direction of arrows 570. Switch plate 560 essentially acts as asliding pinch valve relative to tubular member T₅. Accordingly, when theswitch plate 560 is aligned with the tubular member T₅ in the first area564 of the opening 563, the greatest amount of flow may be allowedthrough tubular member T₅ by the flow diverter assembly 550 (or,conversely, the least amount of flow to the catheter 334). In oneembodiment, this may provide a bleed off of medium flow rate suitablefor use with a 6 French guide catheter (or equivalent flow restrictivestructure). When the switch plate 560 is moved to align tubular memberT₅ within the second area 566 of the opening 563, the tubular member T₅may be pinched (or otherwise restricted in cross-section), therebyrestricting the amount of medium that may flow therethrough, and back tothe reservoir 328 (i.e., the flow in T₅ may be more restricted in thisconfiguration than when the tubular member T₅ is aligned within thefirst area 564 of the opening 563). In one embodiment, this may providea bleed off of medium flow rate suitable for use with a 6 French guidecatheter with a coronary treatment catheter therein, or with a 5 Frenchcoronary diagnostic catheter, wherein a greater amount of flow may bedirected toward the catheter 334. When the switch plate 560 is moved toalign tubular member T₅ within the third area 568 of the opening 563,tubular member T₅ may be further pinched or restricted in cross-section,thereby allowing even less flow of medium therethrough (e.g., throughtubular member T₅) than either of the previous two positions of theswitch plate 560. In one embodiment, this may provide a bleed off ofmedium flow rate suitable for use with a 4 French diagnostic catheter.

The flow diverter assembly 550 need not include merely discretealternate variable flow settings via a mechanism such as movable switchplate 560. Instead, the flow diverter assembly 550 could have amechanism or design that allows variable flow settings including two,three (as shown in FIG. 31) or more selected flow rates for flowdiversion from the syringe 332 to the reservoir 328. In one embodiment,flow diverter assembly 550, tubular member T₄ and stopcock 552 areconfigured as one self-contained component (such as illustrated bycomponent 572 in FIG. 30) that can simply be inserted into the mediumflow path between the syringe 332 and the catheter 334.

Another means for achieving restriction of the driving medium flow ratefrom the syringe 332 is to dispose a flow restrictor in line somewherebetween the syringe 332 and the catheter 334. Such a flow restrictorwould take the form of, for example, a tubular member constrained insize to restrict flow therethrough, a flexible tubular member pinchingmechanism, or a check valve.

One in-line flow restrictor arrangement is illustrated, for example, inFIG. 32. In this embodiment, flow restrictor assembly 550 a is disposeddistally of the manifold 326 and may be similar in configuration to flowdiverter assembly 550 of FIG. 30. As shown, no check valve may beprovided therein, or in association with the medium flow therethrough;however, a check valve could also be provided. Flow restrictor assembly550 a of FIG. 32 is aligned in series along the medium flow path betweenthe syringe 332 and the catheter 334. In one embodiment, the flowrestrictor assembly 550 a may include a switch plate 560 a which ismovable relative to a body 562 a, in the same manner as described abovewith respect to switch plate 560 and base 562. Accordingly, tubularmember T₆ extends from the flow restrictor assembly 550 a and isselectively pinched by manipulation of the switch plate 560 a in orderto selectively restrict medium flow distally from the flow restrictorassembly 550 a, and toward the catheter 334. This arrangement couldprovide an in-line flow resistor along the medium flow path between thesyringe 332 and the catheter 334. In one desired arrangement, a minimumflow rate of 2.5 ml/second delivered to the catheter may be necessary toattain the desired opacity of the medium in the vasculature.

While the medium flow rate modulation schemes illustrated and discussedabove with respect to FIGS. 30-32 provide additional means forinhibiting the introduction of excess medium into the patient over, andduring, an injection profile of such medium, they may be constrained bydesign to preselected flow diversion or restriction relations of theoverall flow of medium from the syringe to the catheter (e.g., splittingthat flow into a 40%-60% relation, as an example). Although the flowdiverter assembly 550 illustrated in FIG. 30 does allow preselectedvariations in the flow rate of medium through the flow diverter assembly550 (by means of the manipulation of switch plate 560), such variationsare achieved by manual manipulation of the switch plate 560. The flowdiverter assembly 550 of FIG. 30 may not automatically compensate fordifferent pressures or injection flow rates introduced by the syringeoperator, as may be seen with the exemplary constant flow modulator 135illustrated in FIGS. 12A and 12B.

FIGS. 33-37 illustrate an alternative flow diverter assembly 575 thatmay compensate for a user injecting short (e.g., one second), hard“puffs” of medium (e.g., during catheter navigation) versus long (e.g.,two seconds or longer), sustained injections (e.g., during vascularvisualization/assessment). Advantageously, diverter assembly 575 mayalso allow an operator to change the injection delivery system (i.e.,guide catheter, stent delivery system, angiographic catheter, etc.)while automatically adjusting the flow of the medium to be sufficientfor opacification (likening the function of the constant flow modulatorof FIG. 12). The flow diverter assembly 575 may change the resistance toflow rate depending upon changes in the pressure applied to the mediumby an operator via the syringe. As resistance is modified to thediverted medium flow rate, the un-diverted flow rate (i.e., the flowrate to the catheter 334) likewise is modified. This arrangement may beuseful for minimizing the amount of medium diverted when a syringeoperator is attempting to introduce a quick “puff” of medium into thepatient. By using a very fast syringe squeeze for that purpose, theoperator will tend to achieve opacity in this arrangement more readilythan, for example, the arrangement of the flow diverter assembly 550 ofFIG. 30. Therefore, flow diverter assembly 575 may be able to reduce thesize of area A in FIG. 4B, as compared to flow diverter assembly 550 ofFIG. 30. With a long, sustained injection, flow diverter assembly 575may act similarly as the flow diverter assembly 550 of FIG. 30, indiverting flow away from introduction to the catheter 334.

The flow diverter assembly 575 may be disposed in the medium flow pathbetween the syringe 332 and the catheter 334, as seen in FIG. 33. In oneembodiment, the flow diverter assembly 575 may be positioned between thesyringe 332 and the manifold 326, fluidly coupled thereto by tubularmembers 578 and 580, respectively. Tubular members 578 and 580 may beconnected to the fittings of a four way stopcock 582, which in turn isconnected by a further tubular member 584 to a valve 586. The stopcock582 is disposed between the syringe 332 and the delivery catheter 334 inthe fluid medium flow path. The stopcock 582 is operably connected tothe syringe 332 such that manipulating the stopcock 582 allows a user toselectively activate and inactivate the flow diverter assembly 575.Valve 586 is operably connected to stopcock 582. In one embodiment, thestopcock 582 and valve 586 may be separate components, coupled via thetubular member 584. In another embodiment, the stopcock 582, tubularmember 584 and valve 586 are configured as one self-contained componentthat can simply be inserted into the medium flow path between thesyringe 332 and the catheter 334. In either configuration, anothertubular member 588 extends from the valve 586 to a medium overflowand/or re-use reservoir 328. In one embodiment, the medium reservoir 328may also serve as the supply reservoir for loading the syringe 332 withmedium. In that arrangement (as illustrated in FIG. 33), syringe 332 isfluidly coupled to medium reservoir 328 by tubular members 590, 580 and578, coupling those components together via a fluid coupling element orassembly. In an exemplary embodiment, the fluid coupling element orassembly includes manifold 326 and stopcock 582. The manifold has amanifold lumen therethrough and includes a first medium port fluidlycoupled to the flow diverter assembly 575, a second medium port fluidlycoupled to the medium reservoir 328, and a third medium port fluidlycoupled to the delivery catheter 334. When the syringe 332 is beingloaded with medium from the medium reservoir 328, the stopcock 582 maybe positioned to permit medium flow between tubular members 580 and 578,but not to tubular member 584 disposed between the stopcock 582 and thevalve 586. Once the syringe 332 is loaded with medium from mediumreservoir 328, then valve B on manifold 326 may be manipulated toprohibit flow back to medium reservoir 328 via tubular member 590, andthe stopcock 582 may be positioned to allow flow through the tubularmembers 578, 584, 580 and manifold 326.

One embodiment of the flow diverter assembly 575 is illustrated in FIG.34, with the components of the valve 586 shown in exploded axialrelation relative to the stopcock 582 thereof. FIG. 35 is a sectionalview of the assembled components of the valve 586 and the stopcock 582illustrated in FIG. 34, while FIG. 36 is an enlarged sectional view of aportion of FIG. 35. The valve 586 includes a diffuser 592 which may beat least partially received within a tubular diverter arm 594 of thestopcock 582. The movable diffuser 592 is activated to move withpressure, and the diverter arm 594 is capable of increasing ordecreasing a medium flow resistance through the diverter arm 594. Thediffuser 592 comprises a radial shoulder 602, and the valve 586comprises a deformable O-ring 596 disposed between the radial shoulder602 and a face 608 of a valve compression plate 604. The valve 586includes a deformable and resilient O-ring 596 that extends over acylindrical extension 598 of the diffuser 592, until it is seatedagainst a radially extending face 600 on a radial shoulder 602 of thediffuser 592. A generally disc-shaped valve compression plate 604 has acentral cylindrical bore 606 therethrough which is larger than the outerdiameter of the cylindrical extension 598 of the diffuser 592. Thecompression plate 604 (as shown in FIG. 35 as being disposed over theextension 598) has a first face 608 that abuts the O-ring 596. Thediffuser 592, O-ring 596 and compression plate 604 are all retained onthe diverter arm 594 of the stopcock 582 by a valve housing 610. In anexemplary embodiment, the valve housing 610 is attached to the diverterarm 594, and the valve housing 610 and the diverter arm 594 define aninternal chamber 616 therein, the internal chamber 616 havinglongitudinal axis therethrough. The valve housing 610 is sealablycoupled to a distal end 612 of the diverter arm 594, as at area 614, toform a single component serving as flow diverter assembly 575. The valvehousing 610 has a first internal chamber 616 for receiving thecompression plate 604, O-ring 596 and a portion of the diffuser 592,including radial shoulder 602. The first internal chamber 616 includes aradially extending face 618 that abuts in generally planer engagementwith a face 620 of the compression plate 604. The first internal chamber616 also includes a cylindrical socket 616 a sized to receive acylindrical projection 604 a of the compression plate 604 therein. Thevalve housing 610 has a second internal chamber 622 which receives aportion of the cylindrical extension 598 of the diverter 592 therein.The second chamber 622 is in fluid communication with the first internalchamber 616 (via the bore 606 in the compression plate 604), and with afitting 624 on the valve housing 610. The fitting 624 is configured forfluid connection to tubular member 588 (e.g., see FIG. 33).

As with the flow diverter arrangement illustrated in FIG. 30, a portionof the injected medium flow from the syringe 332 may be diverted away,in this case by the flow diverter assembly 575. In an exemplaryembodiment, the flow diverter assembly 575 is configured to divert atleast some of the fluid medium within the chamber of the syringe 332 tothe medium reservoir 328 when a threshold pressure level of the fluidmedium within the flow diverter assembly 575 is reached. The divertedmedium flows through a first cylindrical flow channel 650, past anannular check valve seat 652 and into a second larger (in diameter andthus cross-sectional area) cylindrical flow channel 654, all stillwithin an internal chamber 616 of the diverter arm 594 of the stopcock582 (as illustrated by flow arrows 655 in FIGS. 35 and 36). The valve586 further comprises a deformable o-ring disposed between an end of thediffuser 592 and the annular check valve seat 652. The annular checkvalve seat 652, when abutted by the diffuser 592, limits such flow untilsufficient pressure (e.g., a flow diversion threshold pressure level) isexerted by the injected medium to move the diffuser 592 off of theannular check valve seat 652 (thereby overcoming the bias exerted by theO-ring 596 on the diffuser 592). Medium flow continues away from thestopcock 582 through flow channel 654 and around a cylindrical portion656 of the diffuser 592, along a generally tubular flow path. As mediumflow exits the flow channel 654, it may enter the first internal chamber616 of the valve housing 610, and encounter a ramped, radially extendingface 658 of the shoulder 602 of diffuser 592. An outer circumferentialedge 660 of the shoulder 602 has a smaller circumference than an opposedinner circumference of the first internal chamber 616, so flow maycontinue past the shoulder 602 between its circumferential edge 660 andan inner wall of the first chamber 616 (see, e.g., along a generallytubular flow path as illustrated by flow arrows 655 in FIG. 36). Mediumflow may then continue past the O-ring 596 and encounter the compressionplate 604. The face 608 of the compression plate 604 may have one ormore grooves radially extending therein, between its inner opening 606and outer circumferential face 662.

FIGS. 37-41 illustrate an exemplary compression plate 604, with grooves664 a, 664 b and 664 c therein. While a plurality of such grooves areillustrated in FIGS. 37-41, one groove or some other form of surfacediscontinuity may suffice to permit fluid flow across the proximal face608 of the compression plate 604. In the embodiment illustrated in FIGS.37-41 of the compression plate 604, groove 664 a extends radiallyoutwardly across the proximal face 608 of the compression plate 604,from the inner opening or bore 606 therein to its outer circumferentialface 662. The groove 664 a also becomes wider as it radiates outwardly(so that is it wider at the outer circumferential face 662 than at theinner opening 606), with its groove edges 665 a defined by radial linesextending from a central axis of the compression plate 604. In oneembodiment, the arc defined by the groove 664 a is 40 degrees of thecircumference of the compression plate 604. The groove 664 b likewiseextends radially outwardly from the bore 606 of the compression plate604 to its outer circumferential face 662 across the proximal face 608of the compression plate 604. The groove 664 b also becomes wider as itradiates outwardly (so that is it wider at the outer circumferentialface 662 than at the inner opening 606), with its groove edges 665 bdefined by radial lines extending from a central axis of the compressionplate 604. Groove 664 b may be larger than the groove 664 a in oneembodiment, with the arc defined thereby being 60 degrees of thecircumference of the compression plate 604. Groove 664 c is disposed, inthe illustrated embodiment, entirely within 664 b and is defined by apair of parallel groove edges 665 c extending between the bore 606 andthe outer circumferential face 662. The groove 664 c defines a deepergroove channel 666 within the groove channel already formed by thegroove 664 b. In one exemplary embodiment, as illustrated in FIG. 38,centerlines for each of the grooves may be collinear.

Viewing FIG. 35 and FIG. 36 again, medium introduced from the stopcock582 and through the first chamber 616 adjacent the O-ring 596 may flowradially inwardly (between the O-ring 596 and the compression plate 604)via the grooves 664 a, 664 b and 664 c and into the bore 606 which, asnoted above, may have a circumference larger than the outer diameter ofthe distal extension 598 of the diffuser 592. Medium can thus flow alonga generally tubular flow path through the compression plate 604 (via itsbore 606) and around the portion 598 of the diffuser 592 and into thesecond internal chamber 622 of the valve housing 610 (see, e.g., flowarrows 655 in FIG. 36). From there, medium can further flow into thetubular member 588 connected to the fitting 624 on the valve housing610. The medium pressure acting on the compression plate 604 urges itsface 620 against opposed radially extending face 618 of the firstinternal chamber 616, thus creating a barrier to flow by medium past thecompression plate 604, except through the bore 606 (e.g., passing alonggrooves 664 a, 664 b and/or 664 c on face 608 of compression plate 604).

As the pressure is increased in the medium within the flow diverterassembly 575, greater fluid pressure is exerted against the face 658 ofthe diffuser 592, thereby urging the diffuser 592 against the O-ring 596and an end of the valve housing 610. This in turn compresses the O-ring596 against the face 608 of the compression plate 604 and into flowchannels defined by each groove thereon, to reduce the effective channelsize of the grooves and thereby inhibit the flow of medium across theproximal face 608 of the compression plate 604. As the pressure actingon the face 658 of the diffuser 592 increases, the O-ring 596 is furthercompressed and further inhibits the flow of medium past the compressionplate 604. For instance, with respect to the stepped grooves 664 b and664 c, the O-ring 596 may first deform to inhibit flow through shallowergroove 664 b. Further deformation of the O-ring 596 may cause it to theninhibit flow through deeper groove 664 c, progressively. Likewise, aspressure is lessened, the pressure exerted by the diffuser 592 on theO-ring 596 is lessened and more medium is allowed to flow between theO-ring 596 and the compression plate 604 through the flow channelsdefined by the grooves. The diffuser 592 thus “floats” within the flowdiverter assembly 575 in direction of arrows 666 (FIG. 35) and forms afloating valve element that may change the amount of medium flowallowed, depending upon the pressure of the medium flow entering thevalve 586. The diffuser 592 is received within the internal chamber 616,the diffuser 592 being movable along the longitudinal axis of theinternal chamber 616. The diffuser 592, in combination with thedeforming O-ring 596, and face 608 of the compression plate 604, mayform a deforming valve that is pressure compensating for medium flowthrough the flow diverter assembly 575. This arrangement may allow asyringe operator to vary the type of injection of medium using thesyringe 332 (e.g., short puff versus a long, sustained injection), butstill attain flow diversion characteristics that serve to minimize theamount of excess introduction of medium into the patient.

In one embodiment such as illustrated in FIGS. 34-36, the diffuser 592of the valve 586 is formed of a material that may deform at its end,adjacent annular check valve seat 652, to serve as a check valve andprevent fluid flow from the flow diverter assembly 575 back into themain flow line between the syringe 332 and the catheter. In analternative embodiment, such as illustrated in FIGS. 42 and 43, a flowdiverter assembly 575 a is essentially the same in configuration andfunction as the flow diverter assembly 575 described above, except forthe diffuser in valve 586 a. As seen in FIGS. 42 and 43, a modifieddiffuser 592 a may include a O-ring support shank 592 b formed toreceive and retain a deformable and resilient O-ring 592 c thereon. TheO-ring 592 c is thus provided between the end of the diffuser 592 a andthe annular check valve seat 652 (e.g., see FIG. 35) to provide thecheck valve function, described previously.

As may be appreciated, the shapes of the grooves or discontinuities onthe face 608 of the compression plate 604 and the compressibility of theO-ring 596 must be compatible to attain the desired flow controlcharacteristics between those components, when the O-ring 596 iscompressed against the face 608 of the compression plate 604 by movementof the diffuser 592. Changes in the material forming the O-ring 596(either being more or less deformable) relative to the same compressionplate 604 configuration will change the rate of flow modificationdepending upon pressure changes in the fluid medium in the valve 586. Inaddition, while a deformable O-ring in conjunction with a radial facehaving surface discontinuities is illustrated as one embodiment forforming a pressure compensating valve in a flow diverter assembly 575,other variable flow mechanisms may also suffice. For example, a discthat expands dependent upon pressure over an array of medium flow holes,to progressively cover more holes as more pressure from the medium isapplied to the disc or to a related component, will likewise suffice toserve as a flow constrictor. In many cases, full exclusion of mediumflow past the compression plate 604 may not be indicated. Valve 586 mayallow some medium flow therethrough, at all applied fluid pressures,once a minimum pressure threshold is exceeded (such as, again, e.g., 20psi).

It is anticipated that valve 586 may be configured to be adjustable byan operator. For example, medium flow through the valve 586 may bechanged by modifying the size of the flow channel 654, such as bymodifying the diameter of the portion 656 of the diffuser 592 byenlargement/reduction (i.e., mechanically, inflatably, etc.,) therebychanging the effective cross-sectional area of the generally tubularflow path along the diffuser 592. This is but one way that the valve 586may be configured so as to be adjustable, and should not be construed soas to limit the scope of the invention. The capability of adjusting thevalve may allow an operator the ability to make changes mid-procedure(e.g., changing out a diagnostic catheter for a treatment system), asseen, for example, in diverters described in FIGS. 33-43.

FIGS. 52-57 illustrate another medium management system 825 that mayinclude, as shown in the illustrated embodiment, flow diverter assembly575 and a diversion reservoir 827. In this embodiment, tubular member588 a extends from the valve 586 of the flow diverter assembly 575 to amedium diversion reservoir 827, and tubular member 588 b extends fromdiversion reservoir 827 to medium reservoir 328. Medium from the mediumreservoir 328 is permitted to flow away from the medium reservoir 328and through diversion reservoir 827 via tubular members 588 b and 588 a,as well as via tubular member 590. In the illustrated arrangement (seee.g., FIG. 52), syringe 332 may be fluidly coupled to medium reservoir328 by tubular members 588 b, 590, 580 and 578, coupling thosecomponents together by a manifold 326 and through stopcock 582. When thesyringe 332 is being loaded with medium from medium reservoir 328, thestopcock 332 may be positioned to permit medium flow between tubularmembers 580 and 578, but not to tubular member 584 disposed between thestopcock 582 and the valve 586 of the flow diverter assembly 575.Drawing back the syringe 332 may pull medium from the medium reservoir328 through tubular member 588 b, and/or diversion reservoir 827, andthrough tubular member 590. Medium from the medium reservoir 328 maythen be further drawn, into and toward, syringe 332 through tubularmembers 580 and 578. Once the syringe 332 is loaded with medium frommedium reservoir 328, valve B on manifold 326 may then be manipulated toprohibit flow back to medium reservoir 328 via tubular member 590 (andsuch flow may be further inhibited by a check valve disposed betweendiversion reservoir 827 and medium reservoir 328), and the stopcock 582may be positioned to allow flow through the tubular members 578, 584,580 and manifold 326.

As noted above with respect to exemplary modulator systems illustratedin FIGS. 33-43, a portion of the injected medium flow from the syringe332 may be diverted away from the medium flow path to catheter 334 bythe flow diverter assembly 575. In the modulation/reservoir system 825illustrated in FIGS. 52-57, such diverted medium flow passing throughthe flow diverter assembly 575 flows into the diversion reservoir 827,as opposed to flowing directly into the medium reservoir 328 or someother outflow/overflow reservoir/chamber. Advantageously, the diversionreservoir 827 provides means for collecting overflow medium diverted bythe flow diverter assembly 575, for possible re-use as the syringe 332may be again activated to pull medium into the system (e.g., forintroduction into the patient via catheter 334). The use of such adiversion reservoir in this manner, with an associated check valvepreventing back flow of medium into the medium reservoir 328, allows forcapture and re-use of medium that is already introduced into the system(e.g., in the diversion reservoir 827) while preserving the integrity ofthe medium disposed within medium reservoir 328 in its original form.

One embodiment of the diversion reservoir 827 is illustrated in FIGS.53-56. FIG. 53 shows an assembled view of diversion reservoir 827 alongwith its associated tubular members 588 a and 590. FIG. 54 is anexploded view of the assembly of FIG. 53. The system 825 furthercomprises a second supply conduit 590 in fluid communication with thesupply conduit 588 b and the diversion conduit 588 a, wherein the secondsupply conduit 590 is fluidly coupled to the fluid medium flow path.Tubular members 588 a and 590 are sealably connected to a first end capor manifold 835 on diversion reservoir 827, as further shown in FIG. 55,which is a sectional view taken through lines 55-55 in FIG. 53. A firstend of a through-tube 837 is sealably connected to an interior side offirst end cap 835, as at 838. Through-tube 837 includes an inner conduit839 extending therethrough. Inner conduit 839 is in fluid communicationwith the interiors of tubular members 588 a and 590 via their adjacentcouplings in the first end cap 835, as illustrated in FIG. 55. A secondend of through-tube 837 is sealably connected to a check valve assembly841, as at 842, and the inner conduit 839 is in fluid communication withthe check valve assembly 841. The check valve assembly 841 is, in turn,in fluid communication with the tubular member 588 b. As seen in FIG.55, the check valve assembly 841 includes a moveable valve plate 843 (orother suitable structure allowing one way flow through the valve) whichis operable to permit flow from the medium reservoir 328 via tubularconduit 588 b into the inner conduit 839 of through-tube 837, but toinhibit flow in reverse thereof. This arrangement may allow flow ofmedium from fluid reservoir 328 via tubular conduit 588 b, inner conduit839 of through-tube 837, and tubular conduit 590 to the syringe 332.Moreover, medium flow diverted by flow diverter assembly 575 may also bepermitted to flow via tubular member 588 a into inner conduit 839 ofthrough-tube 837, but inhibited from flowing back to the mediumreservoir 328 by check valve assembly 841. A second end cap 844 ondiversion reservoir 827 is secured about the check valve assembly 841.

The diversion reservoir 827 is designed to accommodate such back flow ofmedium from the flow diverter assembly 575, to collect and hold suchmedium and then, if desired, urge such collected medium back into thesystem for use in delivering additional medium to the patient viainjection catheter 334. To accomplish this end, diversion reservoir 827may include an elastic expansion tube 845 disposed about through-tube837. As seen in FIGS. 55 and 56, expansion tube 845 extends along aportion of a length of through-tube 837. In one embodiment, expansiontube 845 is formed of silicone material sealably secured adjacent eachend thereof about the through-tube 837 by first and second retentionwashers 847 and 849, respectively, or by other suitable sealable andmechanical fastening arrangements. An outer surface of the through-tube837 may include interference elements such as surface features or anannular interference rim 837 a (see FIG. 55) to further facilitate thesealing of the expansion tube 845 to the through-tube 837 via theretention washer 847 and 849.

A housing tubular outer shell 855 may be connected between the first endcap 835 and second end cap 844, thereby covering the expansion tube 845and other diversion reservoir components therein. The shell 855 mayserve to protect the components of the diversion reservoir 827 therein,limit the extent of inflation or expansion of expansion tube 845, and/or(if the shell 855 is either transparent or translucent) allowobservation of the condition (e.g., expanded state) of expansion tube845 therein.

FIG. 56 illustrates the diversion reservoir 827 in perspective sectionalview (again, as taken along lines 55-55 in FIG. 53) with the expansiontube 845 shown in an exemplary stretched and expanded state, as opposedto its relaxed state shown in FIG. 55. The expansion tube 845 of thediversion reservoir 827 receives medium flow from the flow diverterassembly 575, via tubular member 588 a. This medium flow, as illustratedby flow arrows 857 in FIG. 56, flows from tubular member 588 a into theinner conduit 839 of through-tube 837 adjacent the first end ofthrough-tube 837. Flow out of the through-tube 837 is inhibited at itssecond end by the check valve assembly 841. However, the supply conduitthrough-tube 837 may have one or more apertures 859 therethrough whichallows an interior of the expansion tube 845 to be in fluidcommunication with the inner conduit 839 and reservoir chamber 860.Medium from the flow diverter assembly 575 can thus flow throughapertures 859 and into a medium reservoir or chamber 860 defined by theexpansion tube 845. This medium chamber 860 is defined between the innersurface of expansion tube 845 and the outer surface of through-tube 837,whereby the expansion tube 845 forms an elastic bladder disposed aroundthe supply conduit 837, with the walls of expansion tube 845 capable ofimparting a force on the fluid medium within the chamber 860. A surfacewithin chamber 860 is capable of imparting a variable or constant forceon the fluid medium within the chamber 860, and the surface is definedat least in part by a wall of the elastic bladder of expansion tube 845.The medium chamber 860 thus receives and collects the diverted portionof the flow of medium from the flow diverter assembly 575. The diversionreservoir 827 comprises a variable or constant force biasing memberdisposed relative to at least one surface within the reservoir chamber860 to urge the surface against the fluid medium within the reservoirchamber 860. The expandable wall of the expansion tube 845 thus definesa surface within the medium chamber 860 capable of imparting a force(variable or constant) on the fluid medium within the medium chamber860. In one embodiment, the second end cap 844 includes an aperture 861therethrough to permit the escape of gas within the cover 855 andthereby readily permit expansion of the expansion tube 845 therein.

In use, as the pressure of medium within the flow diverter assembly 575increases enough to allow flow therethrough, medium flows from the valve586 via the tubular member 588 a to the diversion reservoir 827. Mediumthen flows within the diversion reservoir 827 as illustrated by arrows857 into medium chamber 860, thereby stretching the walls of theexpansion tube 845 and expanding chamber 860 to accommodate the divertedmedium flow. Accordingly, as the medium pressure provided via syringe332 increases in the system, the flow diverter assembly 575 divertsmedium so that the flow to the patient increases as less flow isdiverted by the flow diverter assembly 575 into the diversion reservoir827. The medium contained in the chamber 860 may be available forfurther infusion into the patient via the modulation/reservoir system825. As an example, an operator may activate valve B to allow mediumflow from the chamber 860 of the diversion reservoir 827 into thesyringe 332 (which is being withdrawn to draw such fluid therein). Ifthe fluid needed is greater than the volume retained within the chamber860, the force of check valve 843 is overcome and further medium iswithdrawn from the medium reservoir 328. Once a sufficient amount ofmedium has been withdrawn from the chamber 860 and/or reservoir chamber328, valve B may be closed and the modulation/reservoir system 825 maybe again in condition for delivery of medium via injection catheter 334,by activation of injection syringe 332 by an operator. As long as thestopcock 582 is disposed to allow flow into tubular members 580 and 584,the flow modulator assembly 575 may automatically activate to divertexcess medium, thereby ultimately reducing the amount of mediumintroduced into the patient via injection catheter 334 (e.g., thusintroducing no more medium than necessary to attain operative opacity).Again, as the pressure is increased in the modulator 575, the flow tothe patient is actually decreased by operation of the flow diverterassembly 575. The process can be repeated by an operator as many timesas deemed necessary to complete the procedure desired. Use of themodulation/reservoir system 825 in this manner may achieve theadvantageous reduction of introduction of unnecessary medium into thepatient while achieving the necessary amount and flow of medium in thepatient for diagnostic or treatment means (e.g., for opacity). Inaddition, the diversion reservoir 827 may allow re-use of the divertedoutflow of medium.

The diversion reservoir illustrated in FIGS. 53-56 presents one form ofsuch a reservoir. Alternative forms are contemplated as well. Forexample, an alternative form of elastic bladder or elastic surface maybe provided that functionally allows the receipt of medium overflow fromthe flow diverter assembly 575 into an expansion chamber, and thenfurther allows the flow of medium from the medium reservoir 328 throughthe diversion reservoir 827 and into the modulation/reservoir system 825for use. An alternative means of placing force on the medium within thechamber in the diversion reservoir 827 may be attained by a biasplunger, such as illustrated schematically in FIG. 57. The divertedportion of the fluid medium flows through a diversion conduit 588 a awayfrom the flow diverter assembly 575. The system 825 comprises a mediumreservoir 328 containing a supply source of fluid medium for the system825 and a supply conduit 588 b through the reservoir chamber 834 thatfluidly connects the medium reservoir 328 and the diverter conduit 588a. The supply conduit 588 b comprises a check valve 841 a to prevent theflow of fluid medium from the supply conduit 588 b into the mediumreservoir 328. Diversion reservoir 827 a includes a plunger 828 slidablydisposed in housing 826 and moveable in a linear fashion relative to thehousing 826, as illustrated by movement line 830. Thus, the surface 832is movable in a linear direction relative to the fluid medium within thereservoir chamber 834. A proximal face or surface 832 of the plunger 828thus defines a portion of a chamber 834 within the housing 826 fordiverted medium that is received therein via the tubular member 588 a.

Like the diversion reservoir 827 illustrated in FIGS. 53-56, diversionreservoir 827 a may include a first end cap 835 a that acts as amanifold for medium flow. Tubular member 588 a is connected to first endcap 835 a, as is tubular member 590. Chamber 834 is in fluidcommunication with the interiors of tubular members 588 a and 590, suchas via manifold 836 within the first end cap 835 a, as seen in FIG. 57.A through-tube 837 a is also in fluid communication with the manifold836, and extends through the housing 826 of the diversion reservoir 827a to a check valve 841 a. Check valve 841 a permits medium flow frommedium reservoir 328 via tubular member 588 b into through-tube 837 abut prevents backflow. Medium from the medium reservoir 328 can thenflow from the diversion reservoir 827 a into the syringe 332 via tubularmember 590.

When medium is diverted by the flow diverter assembly 575 into thediversion reservoir 827 a, medium flows as illustrated by flow arrows857 a from tubular member 588 a, through manifold 836, and into thechamber 834. The diversion reservoir 827 a comprises a variable orconstant force biasing member disposed relative to at least one surface832 within the reservoir chamber 834 to urge the surface 832 against thefluid medium within the reservoir chamber 834. In an exemplaryembodiment, surface 832 is planar. The face 832 of the plunger 828 isbiased toward the manifold chamber 836, and thus defines a moveablesurface 832 for the chamber 834 that can move away and expand chamber834 as more medium is introduced therein, when the bias of the forceacting against it is overcome. This bias may be in the form of aconstant or variable force acting on the plunger 828 within the housing826, as illustrated schematically by force arrows 838, and such forcemay be achieved by suitable means such as springs, weight distribution,linear actuator, etc. The use of a linearly moving plunger 828 (as itsmovement is illustrated by arrows 830) may permit more ready measurementof how much medium has actually been diverted by the flow diverterassembly 575 and thereby, by derivation, how much medium has actuallybeen delivered to a patient by the injection catheter 334. The plunger838 thus provides a linear expansion element (surface 832) that servesto apply force to the overflow medium collected for possible re-use inthe chamber 834.

The diversion reservoir 827 a operates in a similar manner to thediversion reservoir 827, discussed above, by providing an expandablechamber for medium diverted by the flow diverter/modulating assembly575, wherein the chamber (e.g., chamber 834, 860) has at least onesurface acting upon it to urge the medium therein back to the flowdiverter assembly 575 for possible re-use. Likewise, medium which hasbeen diverted by the flow diverter assembly 575 into the diversionreservoir chamber 834 is not permitted to flow back to the mediumreservoir 328, via check valve 841 a. In alternative embodiments formodulation/reservoir systems, the diversion reservoir is configured sothat flow through it to the medium reservoir is not permitted ornecessary. One such arrangement is illustrated in FIG. 58, in connectionwith a modulation/reservoir system 825 a. In these arrangements, theremay be no necessity for a through-tube arrangement through the diversionreservoir. The diversion reservoir simply provides an expandable chambertherein for retaining and re-using medium diverted from the flowdiverter assembly 575. Such diversion reservoirs 827 b may employ abladder form of chamber or a constant or variable force resistance formof chamber, such as those illustrated and discussed herein, where atleast one surface therein is capable of imparting a force on the fluidmedium within the chamber. FIG. 58 illustrates an arrangement where themedium reservoir chamber 328 is connected via tubular member 588 c to aT-connector 840 disposed between a diversion reservoir 827 b (without athrough-tube) and the flow diverter assembly 575. The T-connector 840connects at its first end to the tubular members 590 and 588 a, and atits second end to tubular member 588 d that leads to the diversionreservoir 827 b. A side fitting of the T-connector 840 leads via tubularmember 588 c to the medium reservoir 328. A check valve 841 b isdisposed between the T-connector 840 and the medium chamber 328 toprevent back flow of medium from the flow diverter assembly 575 and/ordiversion reservoir 827 b into the medium container 328. In operation,the configuration illustrated in FIG. 58 may be similar to thatdescribed above with respect to FIG. 52. As the pressure of mediumwithin the flow diverter assembly 575 increases enough to allow flowtherethrough, medium flows from the valve 586 via tubular member 588 ato the T-connector 840. Medium may then flow from the T-connector 840via tubular member 588 d to the diversion reservoir 827 b. Mediumflowing into the diversion reservoir 827 b expands the expandablechamber therein to accommodate the diverted medium flow. Accordingly, asthe medium pressure provided via syringe 332 decreases in the system,the flow diverter assembly 575 diverts medium so that the flow to thepatient decreases as more flow is diverted by the flow diverter assembly575 into the diversion reservoir 827 b.

In operation, the configuration illustrated in FIG. 58 may be similar tothat described above with respect to FIG. 52. As the pressure of mediumwithin the flow diverter assembly 575 increases enough to allow flowtherethrough, medium flows from the valve 586 via tubular member 588 ato the T-connector 840. Medium may then flow from the T-connector 840via tubular member 588 d to the diversion reservoir 827 b. Mediumflowing into the diversion reservoir 827 b expands the expandablechamber therein to accommodate the diverted medium flow. Accordingly, asthe medium pressure provided via syringe 332 decreases in the system,the flow diverter assembly 575 diverts medium so that the flow to thepatient decreases as more flow is diverted by the flow diverter assembly575 into the diversion reservoir 827 b.

The medium contained in the expandable chamber within the diversionreservoir 827 b may be available for further infusion into the patientvia the modulation/reservoir system 825 a. To do so, an operatoractivates valve B to allow medium flow from the chamber within thediversion reservoir 827 b into the syringe 332 (which is being withdrawnto draw such fluid therein). If the fluid needed is greater than thevolume retained in the chamber reservoir 827 b, the force of check valve841 b is overcome and further medium is then withdrawn from the mediumreservoir 328. Once a sufficient amount of medium has been withdrawnfrom the chamber within the diversion reservoir 827 b and/or reservoirchamber 328, valve B is again closed and the modulation system 825 a isagain in condition for delivery of medium via injection catheter 334, byactivation of injection syringe 332 by an operator. As long as thestopcock is disposed to allow flow into tubular members 580 and 584, theflow diverter assembly 575 will then again be automatically activated todivert excess medium when a threshold pressure for activation of theflow diverter assembly 575 is attained, thereby ultimately reducing theamount of medium introduced into the patient via injection catheter 334.Again, as pressure is increasing going into flow diverter system 575,the flow through the diverter 575 is relatively decreasing (thus, flowto the patient may be relatively increasing by operation of the flowdiverter assembly 575). The process can be repeated by an operator asmany times as deemed necessary to complete the procedure desired. Use ofthe modulation/reservoir system 825 a in this manner achieves theadvantageous reduction of introduction of unnecessary medium into thepatient while achieving the necessary amount and flow of medium in thepatient for the desired diagnostic or treatment process. Furthermore,the modulating/reservoir assembly may advantageously allow an operatorto change out the injection delivery system (i.e., guide catheter,diagnostic catheter, treatment tools, etc.) without changing the flowmodulator. Moreover, the diversion reservoir may allow simplistic re-useof the diverted medium.

Exemplary Modulation Devices and Methods with Synchronization

In addition to modulating injections by reducing inefficient agent use(as illustrated as areas A, B and/or C in exemplary injection profileQ_(Agent) of FIG. 4B), modulation may also advantageously includedelivering medium to a vessel in greater quantity when there is greaterblood flow, and in lesser quantity when the blood flow is diminished. Itis an objective of at least some embodiments described herein to patternthe injection of medium into a vessel to coincide roughly with thepattern of blood flow in that vessel. By way of example, FIG. 13illustrates an exemplary injection profile delivered by an inventiveinjection system in which the injection profile coincides roughly withthe blood flow within the vessel of FIG. 2. In this case, an average ofabout 2.8 ml/second of agent (e.g., average of Q_(Agent)) may be used tofill the vessel in sufficient quantity (e.g., to perform itsopacification function) while not forcing the vessel to fully fill withagent, or otherwise displacing all of the normal blood flow. Thus, thedotted-line in FIG. 13 highlights the profile produced by the injectionsystem in filling the vessel with medium of about 65% to 85% of thenormal blood flow, for example. The amount needed for mediumconcentration (e.g., within in the blood) may vary depending on theagent and the intended function, and it is possible that suchconcentrations could be provided at as low as 1% of the blood flow rateand at as great as 99% of the blood flow rate without deviating from theintent of the modulation devices and methods described herein.

Synchronized delivery of agent may reduce the risk of “over-filling” thevessels outside of the target vasculature. In addition, such aninjection flow rate profile may provide sufficient agent concentrationwithin the vessel for opacification during lower flow. Over-injectingthe coronary vasculature (for diagnostic or therapeutic purposes) may beseen arteriographically as “blow back” or reflux, and loads the bodywith unnecessary agent(s). Examples of synchronization embodiments mayinvolve sensors and controllers utilized to modulate the injection ofmedium into the target site. Such sensors/controllers might include anEKG (and/or inputs from an EKG) to initiate activation and deactivation,or modulation, of an injector to deliver medium to a vessel as afunction of the pulsatile flow of blood in the vessel. Other embodimentsmay include sensors positioned into, upon, and/or proximate, aninjection delivery catheter so as to infer or deduce a parameter ofblood flow (pressure, flow rate, temperature, velocity, patientrespiration, pH, pO₂, etc.) in an effort to coordinate the injection ofmedium with the flow of blood in the vessel.

Although synchronized delivery will be further elucidated below,coordinating an injection of medium with the flow of blood in a vesselin a varied, or “pulsatile” fashion may not be the only means of usingvaried flow to reduce the amount of medium delivered to the patient,without compromising vascular opacity. Medium injection may also bereduced through pulsatile flow control methods/devices withoutsynchronization. In this regard, pulsatile flow of medium may begenerated by applying rapidly changing pressure (in amplitude over time)to drive a medium delivered to a patient. In this case, the peakamplitude of the pressure wave may be sufficient, or nearly sufficient,to achieve adequate opacity. In a sense, this may be akin to anelectrical model of alternating current (AC) versus direct current (DC)in the application of medium to the patient. The pressure applied to themedium for the patient may be varied in amplitude over many cyclesduring each “pump” of the heart in a coronary artery application. Thepressure may be “pulsed” in a variety of wave forms of design, such as:sinusoidal, symmetrical, and asymmetrical, as examples. As well as, thedesign of the wave may change and/or alternate in frequency, amplitudeor wave size. As previously discussed, graphic illustrations of bloodflow and injection agent flow have been illustrated relative to flowrates (e.g., FIGS. 2, 4A, 4B, 4C, 4D and 13). However, given the directrelationship of flow (Q) and pressure (P) in our model(s), graphicalrepresentation of pressure may also be utilized in characterizinginjection medium modulation techniques. Optimization of delivery ofmedium (such as contrast agent) to a vascular delivery site may beenhanced by control of the medium injection pressure and flow rate.

FIG. 44 illustrates an example of a medium injection pressure profilethat may be found within a left main coronary artery of a humanheart—this may be a typical profile of injection pressure P_(Typical)illustrating an injection profile made by a doctor with a syringeextending over approximately 3.5 seconds, without any modulizationmodification pursuant to the disclosure herein. This profile may besimilar to the injection profile illustrated in FIG. 4A; however, FIG.44 graphically represents a pressure (P) profile, whereas FIG. 4Adepicts a flow rate (Q), over time. FIG. 44 also illustrates anexemplary medium injection pressure profile P_(Modified) for a mediuminjection using a modulation system such as disclosed herein bymodulation system 325 including a variable force delivery platform 402(such as illustrated in FIGS. 26-27). As seen in FIG. 44, the peakinjection pressure along the modulation pressure profile P_(Modified)may be 60 percent less than the typical peak injection pressure withoutmodulation.

FIG. 45 illustrates an exemplary pulsatile medium injection profileP_(Pulsatile I), again over a typical 3.5 second injection of mediuminto a patient. The medium injection profile P_(Pulsatile I) of FIG. 45may allow the attainment of full pressure of a typical injection to berealized, but do so at spaced intervals of medium pressurization. In theexample illustrated in FIG. 45, the “duty cycle” (time between waves)for the pulsatile pressure profile P_(Pulsatile I) may be 0.25 seconds.This is more fully illustrated in FIG. 46, which is an enlarged segmentof a portion of the pressure profile P_(Pulsatile I). In FIG. 46, theportion of each 0.25 second duty cycle where pressure is applied toattain the peak pressure is 0.15 seconds, whereas the portion of eachduty cycle where the pressure is not applied at peak is 0.10 seconds,resulting in a 60% “on”/40% “off” pressurization duty cycle, as anexample of pulsatile injection. It is clear that there are a variety ofwave shapes, peaks, troughs, duty cycles, etc. that one may use toaccomplish a reduction in medium injection without compromising function(e.g., opacification). This is merely one example in the use of apulsatile injection to modulate the delivery of a medium.

FIGS. 47 and 48 illustrate an alternative medium injection pressureprofile P_(Pulsatile II) that illustrates an injection pressure profilesimilar to FIG. 45 but using a different duty cycle for the pulsedmedium pressurization. In this case, the duty cycle is 0.125 seconds,resulting in a higher frequency of pulsation but still attaining apressure P about that of a typical injection P_(Typical). FIG. 48illustrates an enlarged view, showing the exemplary 60/40 duty cycleratio between peaks and valleys of the pulsed flow profileP_(Pulsatile II). Establishing a pulsatile pressure profile for a mediuminjection (such as profiles P_(Pulsatile I) or P_(Pulsatile II)) may notdepend on the peak pressure being applied (such as pressure P in FIGS.44, 45 and 47). Pulsation of medium injection pressure could be appliedto the medium at any desired pressure so as to reduce the reduce theamount of medium injected without opacity compromise

As discussed above with alternative embodiments, modulation of mediumdelivery to a patient may be achieved in parallel, or in series. FIG. 49illustrates schematically an arrangement whereby pulsatile mediumpressure modulation may be achieved in a “parallel” arrangement (wherebythe catheter 334 provides one level of medium flow resistance, and aflow diverter assembly which may include a medium reservoir 700 may, incombination with other diverter elements such as those described above,provide a second resistance to medium flow between the syringe 332 andthe catheter 334). One means for modulating the pressure at the catheteris to modulate the bleed off medium pressure via manipulation ofreservoir 700. In effect, this is achieved by creating a negative pulseon the diverted flow path, like employing a variable resistor thereon.This may be done, for example, by modulating the volume in the reservoir700, such as by means of a movable piston, solenoid or membrane, whichthen has the consequence of changing the frequency of medium pressureapplied to the patient via the catheter 334. The volume in the reservoir700 may be modulated by mechanical forces created by mechanical devices,thereby creating waves or pulses on the medium in the reservoir 700.Such devices can be controlled by a controller 705 coupled to thereservoir 700, either wired or wirelessly via control connection 710.The controller 705 may be located outside the sterile surgical fieldrelative to the patient. Alternatively, a mechanical device may be, bydesign, formed to define a pulsatile action on the medium in thereservoir 700 without requiring a controller 705. The pulsing of thediverted medium flow in an arrangement such as illustrated in FIG. 49may be attained by modulating the volume in the reservoir 700, or alsoby opening and closing a diverter flow path 715 extending between thereservoir and the main flow path between the syringe 332 and thecatheter 334. In either instance, using mechanical or controller drivenmeans to achieve such pulsatile activity relative to the medium in thediverted portion of the medium flow results in likewise reduced mediumflow to the patient via the catheter 334, as illustrated again by theexemplary medium pressure profiles P_(Pulsatile I) (FIG. 45) andP_(Pulsatile II) (FIG. 47). Although these examples describe two ways ofachieving a “pulsatile” pressure, there are a myriad of means to effectsimilar waves and these are not outside the scope of this disclosure.

Moreover, with pulsatile forces acting on a medium in the divertedportion of the medium flow path, the syringe operator may notnecessarily feel the immediate effects of such pulsation (i.e., bytactile sensation when manually manipulating the syringe). To theoperator, the manipulation of the syringe may not feel or function anydifferently than a typical medium injection pressure profile, such asillustrated P_(Typical) in FIGS. 44, 45 and 47.

As noted above, the pressure profile for medium applied to the patientvia the catheter 334 may also be achieved by a pulsatile effect appliedto the medium directly (i.e., in series with medium flow to the catheter334). In this example, a pulsatile generator 720 may be disposed alongthe medium flow line extending between the syringe 332 and the catheter334. The pulsatile generator 720 may be designed to create a positivepulse on the medium flowing therethrough to the catheter 334 in order tovary the pressure of the medium to follow a medium pressure profile,such as illustrated by profile P_(Pulsatile I) (FIG. 45) orP_(Pulsatile II) (FIG. 47). Pulsing of pressure on the medium by thepulsatile generator 720 may be achieved by repetitive pinching of amedium flow line passing through or adjacent, the pulsatile generator720, or by other suitable mechanical flow pulsing means. Alternatively,the pulsatile generator 720 may be incorporated directly into thesyringe 332 so that the fluid flow exiting the syringe 332 is alreadybeing delivered in a pulsed state relative to its pressure profile. Ineither case, the pulsatile generator (whether in line or incorporatedinto or adjacent the syringe), may be controlled by a controller 705disposed outside of the sterile surgical field. The controller 705 maybe coupled, either wired or wirelessly, via control connection 710 tothe pulsatile generator 720, whether the generator is disposed in lineor in the syringe 332. It is also conceivable that the pulsatilegenerator 720 acts independently of any controller.

In many cases of pulsatile flow of medium, the objective is to reducethe amount of medium delivered to the patient, yet still providesufficient medium to achieve operative function. In the case of contrastdelivery, functionality may be determined through opacification of thevasculature upon injection. The advantage of employing a pulsed mediumpressure profile such as those illustrated in FIGS. 45 and 47 is thatthe volume of medium necessary for achieving opacity may be reduced.Also, medium modulation via medium pressure/flow pulsation may not bedependent on the size or form of catheter configurations being deployedin the patient, and thus may provide the ability to further reduce theintroduction of excess medium across all such catheter configurationsand procedures. Furthermore, the effect of “pulsating” the flow ofmedium delivered to a site may provide better “mixing” of agent with theblood and this action, in and of itself, may reduce medium use similarto the “mixing” effect described by the device in FIG. 18

Continuing with “synchronizing” an injection with the flow of blood in avessel, FIG. 14 illustrates exemplary schemas for a synchronized mediuminjection modulation system. As shown, one or more signal sensors 150may each receive a signal representing, deducing, or inferring, thestatus of at least one parameter of flow at the target injection sitesuch as the left coronary arteries of the heart. A controller 152 mayreceive the signal(s) from the sensor(s) 150 and then directly, orindirectly, activate modulated delivery of medium though the deliverycatheter system 154. As can be seen in FIG. 14, valving (or otherwisemodulating mechanisms) may be positioned near the proximal portion ofthe delivery system 154 (e.g., in proximity of the delivery catheterproximal portion, outside of the body, as at proximal valving 156),and/or may be placed in, around, and/or in proximity of the distalportion of the delivery catheter (e.g., inside of the body, as at distalvalving 158), with such valving being actuated by the controller 152.Further, one or more of the sensor signals may be from a sensor locatedexternally of the body such as an EKG, and/or one or more of the sensorsignals may be derived from a sensor within the body (such as a pressuresensor placed in, about and/or in proximity to the distal portion of thecatheter).

Direct control of modulation may include, for example, activating theinjection device directly to synchronize dispensing of medium throughthe injection delivery catheter to produce the injection flow rate(e.g., Q_(Agent)) profile as shown in exemplary FIG. 13. In thisexample, a signal from a sensor 150 (such as, for example, an EKGsignal) is used by the controller 152 to directly actuate the injectorpump 160 so as to increase/decrease the injector output to produce amedium agent injection flow rate (e.g., Q_(Agent)) profile as shown inFIG. 13. An example of such a system may be found in FIG. 15. As can beseen, an EKG signal of the patient's heart rate is received from an EKGsensor 150 by the controller 152. The controller 152 may selectivelysignal a start for increasing flow rate at some time interval after theQRS complex of the EKG, and a start for decreasing flow delivery beforeand/or during the QRS complex, for example. Thus, the controller 152 ofFIG. 15 may then activate/deactivate the pump 160 operably coupled toinjector 162 to varying degrees to provide dispensing of medium from theinjector 162 when an operator has signaled to the controller 152 that aninjection is warranted. The activation/deactivation of the injector pump160 may be capable of producing an exemplary injection profile(Q_(Agent)) as described by FIG. 13.

Indirect control of modulation may include, for example, valving (orotherwise modulating) an injection dispensed from an injection device.As described previously in the various schemas of FIG. 14, indirectvalving (or otherwise controlling mechanisms) may be proximally ordistally positioned within, about, and/or upon the agent delivery system154. An example of an indirect modulation control may be found in FIGS.16A-16D. In this example, a sensor 165 is deployed distally on adelivery catheter 166 (as seen in FIG. 16A) and a modulating device (ofFIG. 16B) is provided proximally (i.e., positioned proximally as shownfor modulator 168 of FIG. 16C, for example). The sensor 165 of FIG. 16Ais an exemplary pressure sensor positioned on the distal tip of thedelivery catheter 166. As described previously, this is only one exampleof the various sensors that may be used in obtaining a signal tosynchronize the delivery of medium with the blood flow rate. Moreover,FIG. 16A illustrates the positioning of the sensor 165 upon the distaltip of the delivery catheter 166. The exemplary positioning of thesensor 165 in FIG. 16A should not be limited to that shown in order toperform the functions described herein, since there may be a multitudeof sensor types (and commensurate signals) positioned at variouslocations on (i.e., as a function of respiration), through (i.e., as afunction of imaging) and within the body (i.e., as a function of avariable proximate a target delivery site). Clearly, even the placementof a distal pressure sensor in exemplary FIG. 16A could take many forms,such as: a pressure wire alongside the catheter; a lumen within thecatheter body for pressure measurement; a pressure sensor deployedwithin the distal tip of the catheter; a pressure sensor deployeddistally of the distal tip of the catheter and into the target vessel,to name but a few.

Referring to FIG. 16B, modulating device 168 may comprise an inlet port170 (from the injection device) and an outlet port 172 (to the deliverycatheter 166). The flow of injection fluid may pass through theinjection port 170 and into a fluid chamber 174 within a body or housing176 of the modulator 168. The modulator 168 may have a plurality ofvane/plates 178 attached to a cylindrical hub 180 disposed within thefluid chamber 174. The vanes 178 and hub 180 may be formed to define a“pinwheel” structure of vane-hub that is capable of rotating freely(relative to fluid chamber 174 and body 176 of modulator 168) upon theinjection of medium into the fluid chamber 174 through the injectionport 170. The hub 180 may be designed to preferentially rotate in onedirection. For example, FIG. 16B illustrates the preferential flow offluid and rotation of the vane-hub, in a clockwise direction, via flowarrows 182. From the fluid chamber 174, injection fluid may flow out ofthe modulator 168 via the outlet port 172.

One advantage of a vane-hub modulator design of this type is that it maybe easy to measure, or otherwise identify, the total volume of injectionfluid delivered through the modulating device 168 (over time) since thevolume of fluid passing through the device 168 during one rotation ofthe vane/hub may be easily determined, and the number of rotationssimply counted by a counting mechanism. Alternatively, each “cell” offluid between adjacent vanes 178 may be readily counted by a countingmechanism. The counting mechanism is not shown in the illustrations, butit may comprise a magnetic, mechanical, ultrasonic, infrared or similarmeasurement device capable of identifying the number of times a vane 178and/or some other element of the vane-hub has passed within its field ofmeasurement, or by determining the number of times the axis of the hub180 has rotated. The output of such a counting device may be utilized todetermine and display (in real-time) the total volume of medium usedduring a procedure. Advantageously, in the management of mediuminjected, an operator/physician may readily see the amount of mediumused (as determined by the counting device and presented by a suitabledisplay or indicative output). The determination of the volume (viacalculations/conversions based on, for example, counted rotations) maybe performed as part of the counting device, or may be performed by adisplay device. In addition to providing volume measurements, thecounting mechanism/signal/display may incorporate various algorithms toalert an operator/physician before, or at a point which, a maximumvolume of agent has been administered (i.e., operator determined value,Maximum Acceptable Contrast Dose, GURM ratio, etc.).

Continuing with the description of the exemplary modulation device 168shown in FIGS. 16B-16C, a vane-hub modulator may comprise twocomponents. One component 186 may be situated adjacent acontroller/actuator 185 and may comprise the input port 170, the outputport 172 and the fluid chamber 174 with rotating vane/hub 178/180. Thiscomponent of the system, which may come into contact with fluids, may bedisposable if so desired. A second component 188 comprising thecontroller/actuator 185, brake mechanism 191, sensor signal 190receiver, and the like may be used to clutch, brake, or otherwiseinhibit the rotation of the vane-hub so as to provide resistance torotation. The resistance induced to the rotation may be coordinated witha signal 190 from sensor 165 of FIG. 16A, so as to modulate an injectionfrom an injector to produce an agent fluid flow (Q_(Agent)) profile asdescribed, for example, in FIG. 13.

The braking, or clutching of the modulator 168 of FIG. 16C may beperformed through a variety of means, to include, for example,mechanical, hydromechanical, electromechanical, electromagnetic,chemomechanical, etc. FIG. 16C illustrates one such means 191 forbraking the shaft 192 of the vane-hub, using electromagnetic means. Theexemplary braking structure 191 is further detailed in FIG. 16D, whereinthe longitudinal shaft 192 of the hub 180 is coupled to a hysteresisplate/disc 194 positioned within a magnetic field 196. When electricityis applied to the magnetic coil 196, a magnetic flux is transferred tothe hysteresis disk 194 (as it passes through the field) causing amagnetic “drag” on the disc 194. The drag, or braking, applied to thehysteresis plate 194 (and thus the shaft 192 of the vane-hub) may beincreased/decreased with increasing/decreasing voltage applied to themagnetic field to modulate the flow of medium as intended. Whenelectrical current is removed, the connected disc/shaft may rotatefreely about an axis of shaft 192. In the example of FIG. 13, themaximum flow rate of agent (Q_(Agent)) is approximately 5.2 ml/second.Therefore, in producing profile of Q_(Agent) of FIG. 13, one might setthe injection of medium into the modulator 168 at a constant rate of 5.2ml/second. Upon modulating, braking mechanism 191 of FIG. 16D mayincrease the drag (reduce the flow rate) of the agent as needed toproduce the flow profile of Q_(Agent) of FIG. 13.

FIGS. 16B and 16C describe one of numerous means to regulate the flowprofile of injection agent thru a modulator, and as such, are intendedto illustrate the modulation monitoring and control concepts disclosedherein without limitation. Of course, such means may be employed withvarious signals and sensors (such as shown in FIG. 16A) to “synchronize”the flow of injection medium with corporeal medium flow. Therefore, theexample of FIG. 16 is but one example how one might use a modulatordevice to perform synchronization.

Previous embodiments of “synchronized” delivery described herein mayinclude active sensing and subsequent modulating of the delivery of amedium. However, delivery of a medium to a delivery site may be alsomodulated by passively valving the medium delivery as a function of aphysical attribute in and/or around the delivery site; such as pressure,for example. Referring to FIG. 23, a delivery catheter 260 may be placedto deliver a medium to a delivery site, such as the left main 24 of thecoronary vasculature. In this setting, there are continuously changingpressures within the left main 24 as well as the aorta 22, as previouslydescribed. A valving mechanism 262 may be deployed within, on or inproximity of the distal portion of the delivery catheter 260.

FIGS. 24A and 24B illustrate in more detail the distal portion of thecatheter 260 with a passive valving mechanism 262 present. As shown inFIGS. 24A and 24B, the valving mechanism may include a blood flow bypasslumen 264, allowing some blood flow alongside medium delivery lumen 266of the catheter 260. A passive valve gate 268 is disposed to limit bloodflow through bypass lumen 264 and medium flow through medium lumen 266,as a function of pressure differential around the delivery site. Asshown in the FIG. 24A, when the pressure within the left main 24 (e.g.,P_(LM)) is less than the pressure in the aorta 22 (e.g., P_(AO)), thevalve gate 268 of delivery catheter 260 may allow the injection ofmedium to the delivery site (as illustrated by medium flow arrows 269 ain FIG. 24A). Conversely, as shown in FIG. 24B, as the pressuredifferential between the left main 24 and the aorta changes 22, with theleft main 24 increasing in pressure with respect to the aorta 22 (e.g.,slowing of blood flow into the left main 24), the passive valve gate 268may act to hinder, or reduce, the delivery of medium to the deliverysite (as illustrated by the medium flow arrow 269 b in FIG. 24B). Thus,the device of FIGS. 23, 24A and 24B provides an arrangement that mayallow “synchronized” delivery of medium to the coronary vasculature as afunction of a passive valve mechanism.

FIGS. 25A and 25B illustrate another embodiment of passively valving thedistal portion of a catheter so as to improve the efficiency of deliveryof medium to a delivery site. FIG. 25A illustrates a delivery catheter270 that may be placed in a sealing relationship (partial or total) witha coronary artery 25 such as, for example, as at catheter/arteryinterface 272. With such use, there may be a concern that blood flowfrom the aorta 22 is restricted from perfusing the occluded artery 25.However, as shown in FIG. 25A, distal portion of delivery catheter 270may have a valve 274 and orifice(s) 276 disposed distally of the valve274 so as to provide perfusion from the aorta 22, through the catheter270, and distal to the delivery catheter (i.e., into the artery 25) whenmedium injection is not taking place. In this instance, valve 274 isclosed, allowing blood to flow into orifice(s) 276, through the distalportion of the catheter 270, and past the catheter/artery interface 272.The valve 274 thus acts to allow blood flow distally, as illustrated byblood flow arrows 278 in FIG. 25A (while inhibiting the flow of mediumpast valve 274). Conversely, as shown in FIG. 25B, when delivery ofmedium is warranted, valve 274 may be deployed so as to reduce perfusionfrom the aorta 22 and allow medium delivery to the delivery site. Inthis instance, valve 274 is open, allowing medium to flow past valve274, through the distal portion of the catheter 270, and past thecoronary/artery interface 272. The valve 274 thus acts to allow mediumflow distally, as illustrated by medium flow arrows 279 in FIG. 25B(while inhibiting the flow of blood past valve 274).

There are many forms wherein the passive distal valving of a deliverycatheter may be employed to further enhance the efficiency and/oreffectiveness of medium delivery to a delivery site. The previousexamples are illustrative of the inventions, and should not beinterpreted as limiting in their scope.

In addition to the various embodiments described herein to effect moreefficient delivery of medium to a target site, the modulation of aninjection may be further enhanced with various delivery catheter tipconfigurations, thus advantageously changing the flow characteristicsin, around and/or proximate the delivery site. For example, FIGS.17A-17D illustrate four embodiments that may be employed to perform sucha function. As previously described by FIGS. 5A and 5B, it is clear thatat least one of the challenges associated with the delivery of mediummay involve the location of the delivery catheter tip and the pressuredifferentials surrounding the tip. FIGS. 5A and 5B illustrate a catheterdelivery tip within the aorta 22, at the ostium 20 to the left main 24.This “catheter tip” placement may be common since physicians may behesitant in delivering the tip of the catheter into the left main due toconcerns of injuring/disrupting the vessel wall and/or causing spasms(and thus acute occlusion) within the left arterial system. If thedelivery catheter is positioned as such, there may be little “drivingforce” (e.g., pressure differential) to preferentially deliver themedium from the delivery catheter tip into the ostium, versus into theaorta (and, thus systemically). FIGS. 17A-17D show various embodimentsthat may preferentially modulate the environment surrounding and/orproximate the delivery catheter tip in order to enhance the delivery ofagent into the ostium. In many regards, these embodiments may also actto isolate/control the environment surrounding the delivery catheterdistal delivery portion so as to accommodate more efficient delivery ofa substance.

For example, FIG. 17A illustrates a delivery device 210 that may have aballoon inflated around its distal portion 212 so as to increase thepressure within the aorta 22 (at least during injection), and further“drive” the injection medium into the ostium 20. The embodiment of FIG.17B illustrates a conical member 222, surrounding the catheter deliverytip of delivery device 220, which may act to capture/isolate medium,and/or increase flow resistance (when deployed) for the medium to flowto the aorta 22; and thus, preferentially “drive” the medium into theleft main 24. P_(AO) and P_(LM) of FIG. 17B designate areas of pressurewithin the aorta (e.g. P_(AO)) and the left main (e.g., P_(LM)) solelyfor the purpose of identification. The conical member 222 may also beexpandable; as well as the expansion of 222 could further be in responseto the pressure gradient between P_(AO) and P_(LM).

The alternative exemplary embodiment described by FIG. 17C shows adelivery device 230 that includes a coaxial member or sleeve 232surrounding a distal catheter delivery portion 234 and may, in essence,act to artificially “extend” the left main 24 into the aorta 22. Thus,upon injection of medium, the flow of the medium is subjected to greaterresistance to flow along the path to the aorta 22 (via the sleeve 232)than would be present flowing to the ostium 20. In some ways, thecoaxial nature of the coaxial 232 member may also advantageouslyfunction as a distal “reservoir” of medium, acting to store and thenrelease medium from the temporary reservoir structure in response to thecyclical pressure changes seen, for example, by the left main 24.

FIG. 17D illustrates another embodiment in the modulation of the flowparameters surrounding the delivery catheter distal portion. As shown, adelivery device 240 has a delivery catheter tip with a coaxiallyexpandable sheath 242 surrounding a distal portion of the catheter. Whenexpanded, the sheath 242 could partially engage the ostium 20, as at 244for example. The expansion of the sheath 242 may be actuated by the flowof injected medium through at least one or more orifices 246 along thedistal portion of the catheter. The expanded sheath 242, when deployed,may create greater resistance to flow (for agent) along the path to theopening 20 of the aorta 22, than along the path into the left main 24,as indicated by the flow arrows in FIG. 17D.

There are many variations to the structures and configurationsexemplified in FIGS. 17A-17D which may modulate, or otherwise control orisolate, the pressure and/or flow environment surrounding a distalportion of the delivery catheter. FIGS. 17A-17D are illustrative ofembodiments that advantageously modulate the flow characteristics in,around and/or proximate the delivery site and, as such, should not beviewed as limiting the scope of the structures and methods for achievingsuch flow characteristics.

In addition to the various disclosed arrangements and processes that mayact to modulate the environ of flow characteristics in, around and/orproximate the delivery site, other delivery catheter distal tip designsmight advantageously “mix” the medium with the blood. The applicantshave found that in at least some medium delivery scenarios (i.e., agent,target site, flow parameters) it may be necessary for the injectedmedium to travel a distance from the distal tip of the catheter beforethe medium may be sufficiently “mixed” with the blood flow (e.g.,homogenous concentration of the medium within the blood). In the exampledescribed by FIGS. 5A and 5B, it is possible that an injected agent maynot reach a homogenous concentration within the blood flow for somedistance distally along the left main and/or arterial supply from theostium. As an example, if it were to take approximately 2 cm to 3 cm forthe medium to mix with the blood, then this distance along the vesselmay not be “well opacified.” In this situation, an operator of aninjector may continue to increase the medium delivery in order to obtaingreater opacification of the vessel. A delivery catheter having a distaltip construction as shown, for example, in FIG. 18 may be able to morereadily mix the medium exiting the catheter with the blood flowing bythe catheter, and therefore may advantageously reduce the amount ofmedium necessary to see the opacification of the artery.

The example of FIG. 18 shows a delivery catheter 250 having ribbedundulations 252 along the inner surface of its distal tip 254 so as toprovide a flow pattern resembling a vortex 256 of the medium exiting thecatheter 250. The disrupted medium flow pattern may more readily mix themedium and blood. Although FIG. 18 illustrates ribbed undulations alongthe inner surface of the delivery catheter, it is clear that there maybe other structures and configurations that may perform the samefunction (such as: structures along the inner and/or outer diameters ofthe delivery catheter; structures deployed within the blood, distal tothe catheter tip, to agitate/disrupt the blood/medium flow; structuressuch as orifices placed along the distal portion of the catheter toallow medium/blood mixing within the delivery catheter; etc.). Inconnection with the notion of mixing the medium and blood, FIG. 18 isonly intended to illustrate an exemplary arrangement and process fordoing so.

Note that “tip” of the catheter as used may be synonymous with the“distal portion,” or any other portion of the catheter that may residewithin the patient's body (e.g., distal of the proximal portion of thedelivery catheter) and might play a role in the delivery of an agent toan intended target site.

In summarizing many of the embodiments described herein, there arenumerous occasions in the diagnostic, prophylactic and treatmentpractice of medicine wherein an agent, substance, material, medicant, ormedium is preferably delivered to a specific site within the body. Someof the examples described herein have advantageously comprised deliverycontrol attributes that may derived from one or more of the modulatingelements/functions illustrated in FIG. 19 (i.e., injection device type,regulation type, sequential versus direct delivery, synchronization withcorporeal flow, activation/deactivation at pump versus after pump, flowenviron manipulation). FIG. 19 attempts to summarize some of thedescribed elements/functions with reference to illustrative FIGS. ofthis disclosure and/or their descriptions. As importantly, the variouselements/functions in media delivery modulation are not, per se,mutually exclusive since one or more of these elements/functions may beused in combination to derive control attributes desired. As such, thevarious elements/functions identified in FIG. 19 may be selected (e.g.,“mix-and-matched”) to produce a modulator that optimally performs anintended purpose. For example, one might consider a variety ofattributes in performance of medium modulating function, such as: targetsite location, target site access, fluid dynamics proximate the targetsite, agent to be delivered (e.g., quantity, viscosity, toxicity),injection frequency, concentration of agent within target site, targetsite isolation, ease of use of modulator, complexity in administration,cost of the system, and cost of agent, to name a few.

FIG. 19 can be considered a general summary for guiding the reader inidentifying an exemplary function/element. Therefore, FIG. 19 is not,per se, inclusive of all the figures and descriptions within thisdisclosure that may contain a particular function/element; nor, is FIG.19 inclusive of all embodiments disclosed herein. It is contemplatedthat the disclosed features, systems and schemes for modulation may becombined in a myriad of combinations and sub combinations to achieveoperative introduction of medium (e.g., opacity) without excessiveintroduction thereof, in addition to those specifically shown anddescribed.

Many of the examples of systems illustrated have involved the deliveryof a cardiovascular contrast agent. However, there are many otherapplications wherein the controlled delivery of a substance to aspecific structure/organ/site of the body may also benefit from thedevices and methods disclosed herein. Due to the variety of medicalapplications, as well as the diversity of means to modulate (forexample, elements/functions of FIG. 19) there may be a multitude ofmechanisms employed to produce a modulator for its unique and intendedpurpose. An example of how one might go about employing variouselements/functions in the construction of a modulator device is furtherdescribed below, as it pertains to a non-cardiovascular procedure oflymphography.

Lymphography employs the delivery of an imaging agent to the lymphaticsystem wherein an agent is injected, and subsequently radiograph(s)taken, in the visualization of metastatic cancer cells. Procedurally(and after identifying the lymphatic), a needle/catheter may be insertedinto a lymphatic channel/vessel in the foot (near the base of the firstmetatarsal) and a contrast medium (such as Ethiodol) may injected intothe body at a very slow rate (approximately 60 to 90 minutes). The totalquantity of injection might be 6-7 ml. The patient typically remains onhis or her back during the procedure. Once the injection is complete,radiographs may be taken. Of note, the “flow” of fluid in the lymphaticsystem is consistently slow, as compared to the high flow andvariability of the coronary arteries. Moreover, the lymphaticchannel/vessels may be very sensitive (e.g., rupture) toover-pressurization.

Given the description of the lymphatic example (and referring to FIG.19), one might construct a modulator with elements/functions thatsatisfy the following attributes: long delivery time; small volumedelivered; constant flow rate; sensitivity to over-pressurization;sufficiently portable/movable to accommodate patient during thedelivery; and, equal to or less expensive than using an automatedinjector. Given these attributes one might consider a manually-loadedinjector device to deliver the medium sequentially (delayed) wherein thedevice may be filled with an amount of fluid to be delivered (e.g., 6ml) first, and upon release of the injection, may deliver the mediumover an extended period of time (e.g., 90 minutes). An element inregulation might include a device with constant flow rate (i.e.,constant flow rate irrespective of variable pressures), or a regulatorelement that functions with constant pressure differentials (i.e.,irrespective of variable flow rates). Because of the high sensitivity topressures in the lymphatic, the latter alternative might be moreamenable in accommodating high pressure “spikes” (for example, if thedelivery catheter were to occlude during the delivery). Viewing FIG. 19,elements of corporeal flow synchronization, flow activation (viasignal), and distal environ alternation may be less important, andtherefore those features may not be included in the exemplary deviceconstruction. Ultimately, a multi-component, sequential delivery deviceas illustrated and described in FIGS. 9A-9C may simply modulate thedelivery of a controlled amount of agent, without the risk of rupturingthe lymphatic channels/vessels due to over-pressurization. Thesequential delivery allows for filling a precise amount of fluid to bedelivered, and once the lymphatic vessel is accessed, may continue todeliver the medium over time.

Clearly, the lymphatic medium delivery is but one additional,non-cardiovascular example and it is intended to help further illustratehow the various elements and components disclosed herein may be used ina variety of ways to satisfy a multitude of clinical applications in thedelivery of a fluidal substance. Moreover, it is anticipated that thesystems described herein may be formed and/or constructed of materialsgenerally recognized to be suitable for medical use, and may includedisposable materials, or reusable materials, or a combination of both inthe construction of components of the system.

It should be understood that the medium delivery modulation devices andmethods described herein are not limited to the particular,representative embodiments as described, since variations may be made tothese embodiments without departing from the scope and spirit of thedisclosure. Likewise, terminology employed in the description ofembodiments is not intended to be limiting and is used merely for thepurpose of conveyance of the concept. Unless defined otherwise, alltechnical and scientific terms used herein have the same meaning ascommonly understood to one of ordinary skill in the art of which thedisclosed devices and methods pertain. In addition, any featuredisclosed with respect to one embodiment may be incorporated in anotherembodiment, and vice-versa.

1. A system for modulating delivery of a fluid medium to a selected sitewithin a patient's body, the system comprising: a syringe for injectingthe fluid medium, the syringe comprising a chamber for receiving thefluid medium therein; a delivery catheter comprising a conduit fordelivering the fluid medium from outside of the body to the selectedsite within the body; a diversion reservoir configured to receive andcontain a portion of the fluid medium for delivery through the deliverycatheter; and a flow diverter assembly disposed in a fluid medium flowpath between the syringe and the delivery catheter, the flow diverterassembly configured to divert the portion of the fluid medium from thechamber of the syringe away from the delivery of the medium through thedelivery catheter conduit and to the diversion reservoir duringinjecting with the syringe, and simultaneously increase medium fluidflow resistance with increasing pressure level of the fluid mediumpassing into the flow diverter assembly.
 2. The system of claim 1further comprising a fluid coupling element having a lumen therethrough,wherein the coupling element includes: a first medium port fluidlycoupled to the flow diverter assembly, a second medium port fluidlycoupled to the chamber of the syringe, and a third medium port fluidlycoupled to the delivery catheter.
 3. The system of claim 1, wherein theflow diverter assembly comprises a check valve.
 4. The system of claim1, wherein the flow diverter assembly is configured to divert theportion of the fluid medium from the chamber of the syringe to thediversion reservoir when a threshold pressure level of the fluid mediumwithin the flow diverter assembly is reached.
 5. The system of claim 1,wherein the flow diverter assembly comprises a mechanism that allows forselection of a level of flow resistance of the fluid medium through theflow diverter assembly.
 6. The system of claim 2, wherein the couplingelement is a stopcock.
 7. The system of claim 2, wherein the flowdiverter assembly comprises a valve operably connected to the couplingelement.
 8. The system of claim 7, wherein the coupling element is astopcock that comprises a diverter arm, and wherein the valve comprises:a valve housing attached to the diverter arm, wherein the valve housingand the diverter arm define an internal chamber therein, the internalchamber having a longitudinal axis therethrough; and a diffuser receivedwithin the internal chamber, the diffuser being movable along thelongitudinal axis.
 9. The system of claim 8, wherein the movablediffuser is activated to move with pressure and wherein the diverter armis capable of increasing or decreasing a medium flow resistance throughthe diverter arm.
 10. The system of claim 8, wherein: the internalchamber comprises: a first flow channel; and a second flow channelhaving a larger cross-sectional area than the first flow channel; andthe diverter arm comprises an annular check valve seat positionedbetween the first flow channel and the second flow channel.
 11. Thesystem of claim 10, the valve further comprising a deformable o-ringdisposed between an end of the diffuser and the annular check valveseat.
 12. The system of claim 8, wherein the valve housing comprises acylindrical pocket, the valve further comprising a valve compressionplate disposed in the cylindrical pocket.
 13. The system of claim 12,wherein the diffuser comprises a radial shoulder, the valve furthercomprising a deformable o-ring disposed between the radial shoulder anda face of the valve compression plate.
 14. The system of claim 13,wherein the face of the valve compression plate comprises adiscontinuity. 15.-17. (canceled)